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Hyperthyroidism: Definition, Causes, Pathophysiology and

Management
Gudisa Bereda1*
1
Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia.
*
Corresponding Author: Bereda G, Department of Pharmacy, Negelle Health Science College, Guji, Ethiopia.
Email: gudisabareda95@[Link]

Citation: Bereda G. Hyperthyroidism: Definition, Causes, Pathophysiology and Management. Journal of

Biomedical and Biological Sciences. 2022;2(1):1-11.

Copyright: © 2022 Bereda G. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.

Received Date: 9th January, 2022 Accepted Date: 22nd January, 2022 Published Date: 31st January, 2022

Abstract
Hyperthyroidism is delineated as the excess secretion and release of thyroid hormone by the thyroid gland
sequencing in improperly high serum levels. Hyperthyroidism can influence multiple organ systems, involving
the cardiovascular, nervous, gastrointestinal, and hepatic systems. The consummate ubiquitous form of
hyperthyroidism is caused by escalated thyroid hormone secretion in Graves’ disease, and the others are toxic
multinodular goiter and solitary toxic adenoma. Graves’ disease is the consummate ubiquitous cause of
hyperthyroidism in developed countries. It is an autoimmune condition in which antibodies against the thyroid-
stimulating hormone receptor cause unopposed stimulation of the thyroid gland. The hypothalamus releases
thyroid-releasing hormone, which stimulates the pituitary to release thyroid-stimulating hormone, in turn
stimulating the thyroid gland to release thyroid hormones, T4 and T3. The escalated secretion of thyroid
hormone normally causes suppression of thyroid-releasing hormone and thyroid-stimulating hormone release
by the hypothalamus and pituitary respectively. Surgical removal of the thyroid gland in patients if with large
gland (>80 g), severe ophthalmopathy, and lack of remission is present. Thyroid surgery is fast and effective but
invasive and expensive. Propylthiouracil and methimazole block thyroid hormone secretion by suppressing the
peroxidase enzyme system of the thyroid gland, thus preventing oxidation of trapped iodide and subsequent
incorporation into iodotyrosines and finally iodothyronine (“organification”); and by inhibiting coupling of
methimazole and diiodotyrosine to form thyroxine and triiodothyronine and also propylthiouracil (but not
methimazole) also inhibits the peripheral transformation of thyroxine to triiodothyronine. Glucocorticoids are
used in thyrotoxicosis in which iodine produces a destroying effect on the thyroid tissue, such as in the initial
phases of subacute thyroiditis or in type-2 amiodarone induced thyrotoxicosis.

Keywords: Causes; Definition; Hyperthyroidism; Management; Pathophysiology

Introduction thyroid hormone secretion and in the adult the

recommended daily iodine uptake is 150 mg. Excess
Thyroid hormones deed on nearly entire nucleated cells iodine ingestion (up to 150 mg/d) also decreases the
and are crucial for normal growth and energy release of thyroxine (T4) and triiodothyronine (T3)
metabolism [1]. Iodine is a crucial requirement for from the thyroid resulting in small decreases in serum
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T4 and T3 concentrations with compensatory increases 10%, is excreted in the stool. In person with normal
in basal and TRH stimulated thyrotropin (TSH) thyroid work, this pathway of T4 and T3 recirculation
concentrations, all values remaining well within the contributes so fewer to hormone presence that patients
normal range [1]. The sophisticated inverse who have gastrointestinal disease or are taking
consociation between the pituitary derived thyroid medications that de-escalate T4 absorption do not have
stimulating hormone (TSH) and the thyroid hormones, anomaly thyroid work. However, the thyrotoxic states
free thyroxine (FT4) and free tri-iodothyronine (FT3), are described by an escalated enterohepatic circulation
renders TSH the further sensitive marker of thyroid of thyroid hormones, as well as by an escalated urinary
status [2]. Hyperthyroidism is delineated as the excess and fecal excretion of both conjugated and free T4.
secretion and release of thyroid hormone by the thyroid Thyroiditis, inflammation of the thyroid gland
gland sequencing in improperly more serum levels. The sequencing in release of stored hormone, is an often
disproportionate quantum of thyroid hormone antecedent of thyrotoxicosis. The clinical presentation
influences to an enhanced metabolic state [3]. of thyrotoxicosis varies from asymptomatic
Hyperthyroidism is a ubiquitous situation with a broad (subclinical) to life threatening (thyroid storm).
difference in the narrated occurrence, reflecting several Thyroid storm is a real endocrine emergency. In thyroid
factors such as variations in dietary iodine uptake, storm there is hyper metabolism, and excessive
ethnical origin, and population structure. adrenergic activity, death may occur due to heart failure
Hyperthyroidism is the consummate ubiquitous and shock. Hyperthyroidism is consummate ubiquitous
antecedent of thyroid dysfunction in areas with mild among women and affects around 2% of women and
and moderate iodine deficiency [4]. Occurrences are 0.2% of men. The consummate ubiquitous form of
seen at entire ages but presentation peaks between hyperthyroidism is antecedent by escalated thyroid
twenty and fifty years of age 2ndry to the higher hormone secretion in GD, and the distinctive are
prevalence of Graves’ disease. TMG typically happens TMNG and STA [6, 7]. Nodular thyroid disorders are
after age fifty years, as opposed to toxic adenoma, further prevalent in iodine deficiency while
which presents at a younger age. All forms of thyroid autoimmune thyroid disorders involving Hashimoto’s
disease are consummate ubiquitous in women [3]. thyroiditis and Graves’ disease happen consummate
Subclinical hyperthyroidism is delineated by a serum often in iodine-replete populations. However, a variety
TSH level that is beneath the statistically delineated of distinctive peril factors involving genetic and ethnic
lower limit along with a serum free thyroxine (fT4) susceptibility, gender, smoking, alcohol consumption,
level within the normal reference range. Its prevalence availability of distinctive auto-immune conditions,
is greater in iodine-inadequate areas, and although it syndromic conditions and drug exposures also lead
escalates with age, it still is comparatively ubiquitous in thyroid disease epidemiology [1].
women of childbearing age [5]. Hyperthyroidism can
influence many organ systems, involving the Graves’ disease: Graves’ disease is the consummate
cardiovascular, nervous, GI, and hepatic systems. The ubiquitous antecedent of hyperthyroidism in developed
interaction between the thyroid and liver is countries. It is an autoimmune condition in which
hypercritical for sustaining homeostasis in both sites. antibodies against the TSH receptor cause unopposed
Thyroid hormones are glucuronidated and sulphated enliven of the thyroid gland. Graves’ disease influences
within the liver and subsequently excreted into bile; around 0.5% of the population, dominantly patients in
furthermore, these hormones sustain the metabolism of the age group forty to sixty years with a female to male
bilirubin by playing a function in the enzymatic activity ratio of 5:1 to 10:1. Circulating thyroid antibodies
of glucanosyltransferase and by regulating the degree initiate the TSH receptor and enliven thyroid follicular
of ligandin, a preponderance organic anion-binding hypertrophy and hyperplasia with escalates in thyroid
protein [6]. A very small portion of the daily production hormone secretion. Graves’ disease is described by
of thyroxin (T4) and triiodothyronine (T3), less than hyperthyroidism and diffuse goiter; ophthalmopathy,
pretibial myxedema and thyroid acropachy perhaps
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antecedent. The pathogenesis of this enigmatic Toxic multinodular goiter is an indispensable

condition remains incompletely understood but the antecedent of hyperthyroidism. It is caused by
central pathogenetic event is the unregulated unwarranted release of thyroid hormones from many
stimulation of the TSH receptor by autoreactive TSH autonomously working nodules in the thyroid gland. It
receptor antibodies (TRAbs). Graves’ disease has been is further ubiquitous in sections of dietary iodine
described throughout the globe and predominantly deficiency (third-world countries) and in the geriatrics
affects women (female: male ratio 8:1), typically in (poor diet). TMNG is more common than Graves’
their 3rd to 5th decades of life [1, 8]. Individuals with a disease in the elderly [3].
family history of hyperthyroidism or distinctive
autoimmune diseases such as pernicious anemia, Toxic nodular goitre (toxic adenoma): Toxic nodular
myasthenia gravis, T1DM, and celiac disease have an goiter is the consummate often antecedent of
escalated propensity of advancing Graves. thyrotoxicosis in the elderly, especially in iodine
deficient areas. Solitary toxic nodules are further
Pathogenesis Graves’ disease: The cause of Graves’ ubiquitous in women than in men with a 1:5 M: F ratio
disease remains unknown, but it is believed to sequence reported in some studies. An autonomous thyroid
from a complex interaction between genetic nodule (toxic adenoma) is a discrete thyroid mass
background (heredity), environmental factors and the whose function is independent of pituitary control [1,
immune system. For not well-known rationale, the 10].
immune system secretes antibodies [TSH receptor
Subacute thyroiditis: Thyroiditis is described by a
antibody (TRAb)] that enliven the thyroid gland to
self-limiting course of thyrotoxicosis, followed by
secrete excess thyroid hormone. Genetic susceptibility
hypothyroidism, and then return to normal thyroid
to the disease is considered to be polygenic. Graves’
work or is inflammation of the thyroid gland that
disease has been narrated to be consociated with the
typically follows a viral upper respiratory infection and
human leukocyte antigen (HLA) gene on chromosome
causes additional release of preformed thyroid
6p, the cytotoxic T lymphocyte antigen-4 (CTLA-4)
hormone. It is slightly further ubiquitous in females
gene on chromosome 2q33, and the lymphoid tyrosine
than males (ratio of 1.5:1) and permanent
phosphatase (PTPN22) gene on chromosome 1p13. In
hypothyroidism occurs in 10-20% of cases. Acute
Graves’ disease, hyperthyroidism sequences from the
painful thyroiditis often presents following a
action of thyroid-stimulating antibodies (TSAb)
respiratory tract infection, while painless thyroiditis
directed fight the thyrotropin receptor on the surface of
perhaps happens post-partum in up to 9% of otherwise
the thyroid cell. The thyroid-stimulating
normal women [1, 11].
immunoglobulin (TSI) attaches to and enliven the TSH
receptor on the thyroid cell membrane sequencing in Suppurative thyroiditis: Suppurative thyroiditis is an
follicular cell growth, vascularity escalates, and in infection of the thyroid gland typically antecedent by
excessive secretion and secretion of thyroid hormone. bacteria but can be antecedent by fungus, mycobacteria,
The thyroid gland typically replaces lymphocytic or parasites. It is consummate ubiquitous in
infiltration, with T-lymphocyte deformity and absence immunocompromised individuals or those with
of follicular diminishment. T cells activate local underlying thyroid disease. It presents with a tender
inflammation and tissue remodelling by secreting and erythematous anterior neck mass, fever, dysphagia, and
releasing cytokines, leading to B-cell dysregulation and dysphonia [3].
increase in autoantibody production. An unbalance
between pathogenic and regulatory T cells is considered Drug induced hyperthyroidism: Amiodarone-
to be involved in both the development of Graves’ induced hyperthyroidism (AIH): Amiodarone, a
disease and its severity [9]. benzofuranic derivative containing 75 mg of iodine per
200-mg tablet, is broadly used for the long-term
treatment of cardiac arrhythmias. Amiodarone inhibits
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the 5’monodeiodination of T4 in the liver and pituitary, the elderly who may have coexisted cardiac disease and
hence decreasing serum T3 and mildly increasing also to those with limited access to healthcare [1, 13].
serum T4 levels without altering TSH concentrations. Iodide-induced hyperthyroidism perhaps happen in
Type 1 AIT is due to the high iodine content of patients with iodine-deficiency goiter, in euthyroid
amiodarone. It happens in areas of iodine deficiency Graves’ disease patients after antithyroid medication
and in patients with underlying thyroid disorders, such treatment, in euthyroid subjects with former
as multinodular goiter. In Type 1 AIT, the thyroid gland instantaneous and iatrogenic episodes of thyroid
secretes and releases excessive quantum of thyroid malfunction, in patients with multinodular goiters who
hormone. In contrast, Type 2 AIT sequences from a reside in sections of iodine repletion or inadequacy and
destructive process in the thyroid gland in which settled in person with no confirmation of underlying thyroid
thyroid hormones leak from the injured follicular cells disease [2].
in patients without underlying thyroid disease.
Amiodarone induced thyrotoxicosis is consummate Postpartum thyroiditis: Postpartum thyroiditis is
ubiquitous in iodine deficient areas and appears to be inflammation of the thyroid gland following delivery. It
consummate ubiquitous in men [1, 12]. Amiodarone- is a transient form of hyperthyroidism that can advance
induced hyperthyroidism (AIH) is much more common six weeks to six months postpartum with an important
and challenging to treat than amiodarone-induced chance of recurrence in subsequent pregnancies.
hypothyroidism. Amiodarone-induced thyrotoxicosis Patients present with painless goiter and typically have
results from two different mechanisms. The iodine important family history of autoimmune disease [3].
released during the metabolism of the drug is
accountable for the thyrotoxicosis in consummate Pathophysiology
cases. Predisposing factors involve micronodular and
The secretion and release of thyroid hormones is
macronodular goiter, which are ubiquitous in older
regulated by a sensitive negative feedback loop
patients who consummate frequently necessitate
including the hypothalamus, pituitary gland, and
amiodarone. Thyroid autoimmunity has also been
thyroid gland. The hypothalamus releases TRH, which
incriminated as a predisposing factor and antithyroid
enliven the pituitary to release TSH, in turn stimulating
antibodies have been resulted following amiodarone
the thyroid gland to release thyroid hormones, T4 and
administration in some patients but not in others [3].
T3. The increased synthesis of thyroid hormone
Other drugs that antecedent thyrotoxicosis involve
normally causes inhibition of TRH and TSH release by
interferon-α, lithium, tyrosine kinase inhibitors, highly
the hypothalamus and pituitary respectively. Disruption
active antiretroviral therapies, immune checkpoint
of this delicate system leads to additional secretion and
mediators and the humanized monoclonal antibodies
release of thyroid hormone and subsequent
used in the management of multiple sclerosis. Although
hyperthyroidism. TSH-secreting pituitary tumors
these drugs may cause transient thyrotoxicosis through
release biologically active hormone that is
destructive thyroiditis the immune modifying agents
unresponsive to normal feedback control. The tumors
such as interferon-α, HAART, and alemtuzumab may in
perhaps co-secrete prolactin or growth hormone;
addition induce Graves’ diseases through less well-
thereupon, patients perhaps available with amenorrhea,
defined immune reactivation mechanisms [1].
galactorrhea, or signs of acromegaly. Hyperthyroidism
Iodine induced hyperthyroidism: Iodine-induced usually occurs with larger nodules (>3 cm in diameter).
hyperthyroidism, the Jod-Basedow phenomenon, is Thyrotoxicosis occurs when the autonomous follicles
common in geriatric peoples with long standing nodular generate more thyroid hormone than is required. The
goitre and in regions of chronic iodine deficiency secretion of thyroid hormones in the thyroid gland
undergoing iodine supplementation. Iodisation depends on iodine. Dietary iodide is transported into
programs temporarily increase the risk of iodine cells and transformed to iodine. The iodine is then
induced hyperthyroidism; the risks are principally to attached to thyroglobulin by thyroid peroxidase and

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subsequently forms monoiodotyrosine (MIT) and hyperthyroidism are: to normalize the production of
diiodotyrosine (DIT). The MIT and DIT are coupled to thyroid hormone; minimize symptoms and long-term
form T4 and T3 respectively. T3 is further biologically consequences; provide individualized therapy based on
active and is typically formed in the periphery by type and severity of disease, patient age and gender,
transformation of T4 to T3. In the serum, thyroid existence of non-thyroidal conditions, and response to
hormone is typically attached to protein and inactive. previous therapy. Treatment strategies include
Any process that escalates the quantum of unbound antithyroid drugs, radioactive iodine, thyroid surgery,
(free) thyroid hormone has the potential to antecedent and medications for symptom control.
thyrotoxicosis [3, 7].
Non-Pharmacologic Therapy
Clinical Manifestations
Surgical takeoff of the thyroid gland in patients if with
Symptoms of thyrotoxicosis involve nervousness, large gland (>80 g), severe ophthalmopathy, and lack of
anxiety, palpitations, emotional lability, easy remission is present. Thyroid surgery is rapid and
fatigability, heat intolerance, loss of weight concurrent effective but invasive and expensive. Patients need to
with an escalated appetite. Physical signs of be euthyroid before surgery. It can cause permanent
thyrotoxicosis perhaps involve warm, smooth, moist hypothyroidism and transient hypocalcemia requiring
skin and unusually fine hair, separation of the ends of calcium supplementation. Surgical complications
the fingernails from the nail beds (onycholysis), include recurrent laryngeal nerve affliction and
retraction of the eyelids and lagging of the upper lid permanent hypoparathyroidism. Because of the efficacy
behind the globe upon downward gaze (lid lag), of antithyroid drug and radioactive iodine therapy,
tachycardia at rest, widened pulse pressure, and a surgery is performed less frequently. It is particularly
systolic ejection murmur; sometimes gynecomastia in reserved for pregnant women intolerant of thioamides,
men [1]. children with severe disease, severe ophthalmopathy,
amiodarone-induced refractory disease, or unstable
Diagnosis cardiac conditions. In the past, stress in the operating
room during surgery was the consummate ubiquitous
An elevated 24-hour radioactive iodine intake (RAIU) antecedent of thyroid storm, with a mortality of 50%.
describes true hyperthyroidism: the patient’s thyroid Thyroid storm during surgery is exceedingly rare now
gland is overproducing T4, T3, or both (normal RAIU with preoperative therapies including propranolol,
10% to 30%). TSH-induced hyperthyroidism is antithyroid medication, and iodine. If thyroidectomy is
diagnosed by evidence of peripheral hyper-metabolism, planned, propylthiouracil or methimazole is usually
diffuse thyroid gland enlargement, accelerated free given until the patient is biochemically euthyroid
thyroid hormone levels, and accelerated serum (usually six to eight weeks), followed by the addition of
immuno-reactive TSH concentrations. TSH-secreting iodides (500 mg/day) for 10 to 14 days before surgery
pituitary adenomas are diagnosed by demonstrating to de-escalate the vascularity of the gland.
lack of TSH response to thyrotropin-releasing hormone Levothyroxine perhaps added to sustain the euthyroid
stimulation. In thyrotoxic Graves’ disease, there is state while the thioamides are continued. Propranolol
escalate in the overall hormone production rate with a can be used for several weeks preoperatively and seven
disproportionate increase in T3relative to T4 [4]. to ten days after surgery to maintain a pulse rate less
than 90beats/min [3].
Treatment
The objective of management is to monitor the situation
Antithyroid Pharmacotherapy
of hyperthyroidism using medical, radioiodine or The mainstay of drug therapy is suppression of thyroid
surgical treatment. Therapeutic objectives for hormone synthesis with thioamides. The duration of

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antithyroid medications is considered to be twelve to twenty hrs [14]. The launching dose of CBZ/MMI is
eighteen months. ordinarily between 20 to 40 mg/day based on the
severity of the hyperthyroidism. PTU launched at
Thioamides between 100 to 150 mg 3 times a day with 100 mg of
PTU thought equal to around 10 mg of CBZ/MMI. The
The consummate commonly used antithyroid drugs are primary high dose of the medications can be tapered
the thioamides, PTU and MMI. PTU and MMI obviate down after four to eight weeks in what is referred to as
thyroid hormone generation by suppressing the the titration regimen. A maintenance dose of 5 to 20 mg
peroxidase enzyme system of the thyroid gland, thus of MMI or equivalent is achieved by about four to six
preventing oxidation of trapped iodide and subsequent months and this is continued for twelve to eighteen
incorporation into iodotyrosines and finally months. The block–replace regimen refers to the
iodothyronine (“organification”); and by suppressing alternative of sustaining the high dose of antithyroid
coupling of MIT and DIT to form T4 and T3 and also medications while adding levothyroxine to sustain
PTU (but not MMI) also inhibits the peripheral euthyroidism [17]. The rationale use of MMI as a first-
transformation of T4 to T3. MMI and PTU are actively choice antithyroid is preferable for the following
concentrated by the thyroid against a concentration reasons: a further quick normalisation of serum thyroid
gradient. Their primary effect is to inhibit the intra- and hormone levels, less frequent occurrence of major, life-
extra-thyroid hormonal synthesis. Intra-thyroid effects threatening side effects and broader presence (PTU is
act through inhibition of iodide organification, not present in multiple countries) [17].
inhibition of iodide incorporation in the tyrosine
residues of thyroglobulin and inhibition of pairing of The adverse drug reactions of MMI and PTU: Minor
iodothyrosines. Extra-thyroid effects act through adverse reactions include pruritic maculopapular
inhibition of the transformation of T4 to T3, due to the rashes, arthralgias, fever, and a benign transient
blocking of deiodinase-type-1 action. It has been leukopenia (<4,000/mm3). Major adverse effects
narrated that PTU, but not MMI, reacts with the include agranulocytosis (with fever, malaise, gingivitis,
selenenyl iodide intermediate of deiodinase-type-1 to oropharyngeal infection, and a granulocyte count <250/
form a selenenyl sulfide and thereupon blocking the mm3), polymyositis, GI intolerance, hepatotoxicity,
transformation of T4 to T3 during the and hypoprothrombinaemia. If it occurs,
monodeiodination reaction and inhibition of thyroid- agranulocytosis almost always develops in the first
hormone transcriptional outcomes, owing to the three months of therapy; routine monitoring is not
impaired attached to T3 nuclear receptors and to the recommended because of its sudden onset [18].
recruitment of co-suppressor, and / or to the
Propylthiouracil Methimazole
dissociation of co-activators [14-16]. Antithyroid Has inhibition of thyroid Has inhibition of thyroid
medications can be used both in the initial management peroxidase peroxidase
of hyperthyroidism (long-term therapy: one to two No inhibition of T4 to T3 Has inhibition of T4 to T3
year) and as a preparation for radiometabolic or surgical conversion conversion
management (short-term therapy: weeks or months). High albumin binding Low albumin binding
The elective indications for pharmacological treat are: Half-life (1-2 hours) Half-life (6-8 hours)
mild or moderate hyperthyroidisms, slight escalate of Duration of clinical action Duration of clinical action
gland volume, children or adolescent age, pregnancy or (12-24hours) (40 hours)
Has minor intrathyroidal Has major intrathyroidal
breast-feeding, and ophthalmopathy that could be storing storing
worsened by radiometabolic treatment. The serum t1/2 Time to reach normal Time to reach normal
of MMI is six to eight hrs whereas the t1/2 of PTU is serum hormone levels (10- serum hormone levels (2-4
one to two hrs. Furthermore, MMI has been resulted to 15 weeks) weeks)
have measurable intrathyroidal concentrations up to Worse patients’ Better patients’
compliance compliance
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Table 1 difference between propylthiouracil and methimazole

Antithyroid Drugs of Second
Radioactive Iodine Therapy Choice
Potassium Perchlorate
Radioactive iodine (131I) is the consummate
ubiquitously used form of management in the United Perchlorate is the dissociated anion of perchlorate salts.
States. It is safe, the principal adverse drug reaction It is rapidly absorbed from the GIT after oral
being the early or late advancement of hypothyroidism, administration. Perchlorate can be used in the
requiring life-long thyroid hormone replacement management of thyrotoxicosis due to excess of
following 131I treatment. Radioactive iodine therapy exogenous iodine, particularly in type1 amiodarone-
can be used in Graves’ disease, toxic nodules, and induced thyrotoxicosis. The drug competitively
TMNGs. It is the consummate ubiquitous form of suppresses iodide uptake in the thyroid gland by
therapy for adults with Graves’ disease. Therapy is competitively attaching with NIS and also has the
provided by a single oral dose of radioactive iodine that capability to discharge iodine from the thyroid gland,
is absorbed by the thyroid gland and causes organ- decreasing intrathyroidal iodine, thereby reducing
specific inflammation. Continuous radiation to thyroid thyroid hormone generation and accelerates its release.
cells sequences in extensive local destruction and The initial dose is 250 mg every six hour by oral
thyroid gland is ablated over a period of six to eighteen administration. It must be underlined that this substance
weeks. Treatment with 131I does not cause a decrement can secrete many side effects, among which the most
in fertility and does not cause cancer, nor has it been serious is bone-marrow depression, which can
revealed to secrete ill outcomes in offspring of those so influence to medullary aplasia. Perchlorate side effects
treated prior to pregnancy. It is contraindicated during are gastrointestinal irritation, rashes, drug fever,
pregnancy. The aim of RAI treatment is to destruct lymphadenopathy, nephrotic syndrome, and
adequate thyroid tissue to heal hyperthyroidism by agranulocytosis [14, 17, 20].
rendering the patients either euthyroid or hypothyroid.
Although it is mostly effective, with a heal rate
approaching 100% after one or further treatments, it has Beta Blockers
confirmed impossible to titrate doses for individual
Multiple of the symptoms of hyperthyroidism such as
patients accurately to guarantee a euthyroid state [19].
sweating, anxiety, tremor and palpitations are
RAI management is effective in pediatric with
antecedent by escalated sympathetic activity and can be
hyperthyroidism owing to GD, and consummate
controlled promptly by beta blockers. Propranolol in
patients can be successfully managed with a single oral
relatively high doses of over 160 mg per day can mildly
dose. Radioactive iodine should be seen at four- to six-
suppress transformation of T4 to T3. Administering
week intervals for the first three months following
beta blockers such as atenolol 50 to 100 mg or nadolol
radioactive iodine treatment, and then at intervals as the
40 to 80 mg once daily can be used to ameliorate
clinical situation dictates. Sodium iodide 131 is an oral
medication compliance. In the absence of
liquid that concentrates in the thyroid and primarily
contraindications such as asthma, beta blockers are
impairs hormone secretion by incorporating into
used in the first few weeks of managing
thyroid hormones and thyroglobulin. Over a period of
hyperthyroidism while awaiting the outcome of
weeks, follicles that have received up RAI and
antithyroid drugs. They perhaps used when antithyroid
surrounding follicles advance confirmation of cellular
drugs are discontinued for managing with RAI. Rate-
necrosis and fibrosis of the interstitial tissue. RAI is the
limiting CCBs perhaps used if there are
agent of choice for Graves’ disease, toxic autonomous
contraindications for beta blockers [17]. β-Blockers are
nodules, and toxic multinodular goiters. Pregnancy is
ordinarily used as adjunctive therapy with antithyroid
an absolute contraindication to the use of RAI [3, 17].
medications, RAI, or iodides when managing Graves’

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disease or toxic nodules; in preparation for surgery; or not the 1st-line management of type 1 amiodarone-
in thyroid storm. It is initial treatment solely for induced thyrotoxicosis (AIT), but few studies have
thyroiditis and iodine-induced hyperthyroidism. βBs used lithium as adjuvant treatment. Side effect of
are contraindicated in patient with decompensated heart lithium carbonate is symptoms of chronic intoxication
failure sinus bradycardia, coincident treatment with can be classified to mild, moderate, and severe toxicity.
MAOIs or tricyclic antidepressants, and patients with The symptoms of mild toxicity (lithium level 1.5–2
spontaneous, hypoglycemia. Side effects of beta mEq/L) involve nausea, vomiting, diarrhea, hand
blockers includes hypersensitivity reactions (skin tremor, and drowsiness while the symptoms of
rashes, drug fever, rhinitis, conjunctivitis), salivary moderate toxicity (level 2–2.5 mEq/ L) include
gland swelling; “iodism” (metallic taste, burning mouth myoclonic twitches, nystagmus, dysarthria, ataxia, and
and throat, sore teeth and gums, symptoms of a head confusion. Severe toxic symptoms (level > 2.5 mEq/L)
cold, and sometimes stomach upset and diarrhea); are renal failure, injured consciousness, seizure, coma,
gynecomastia [14]. and death. Precipitating factors of chronic lithium
toxicity might be escalate in the dose of the lithium
Lithium Carbonate regimen, a decrement in renal work decrement, or
receival of certain drugs such as thiazides, NSAIDs,
There are two lithium carbonate preparations, namely, and ACEIs. These drugs escalate renal reabsorption of
immediate-release and sustained release. The lithium, causing escalated serum lithium concentration.
immediate-release and sustained-release preparations However, toxic symptoms may occur even in the
reach a peak plasma concentration at about 1-2 hours therapeutic range of lithium [17, 20].
and 4-5 hours after administration, respectively. The
elimination t1/2 of lithium is about 18–36 hours, and it Glucocorticoids
is consummately excreted by the kidneys. Lithium
clearance is thought-out to de-escalate with aging and The main mechanism of glucocorticoids in controlling
renal impairment. Lithium is concentrated by the thyrotoxicosis is their inhibitory effect on peripheral T4
thyroid gland at a degree three to four folds of that in to T3 conversion. Glucocorticoids are used in
the plasma, likely by active transport. The initial thyrotoxicosis in which iodine produces a destroying
mechanism of lithium is the suppression of thyroid effect on the thyroid tissue, such as in the initial phases
hormone release by obviating the action of TSH on of subacute thyroiditis or in type-2 amiodarone induced
cAMP. Lithium perhaps also suppresses thyroid thyrotoxicosis. Type 2 AIT is managed with oral
hormone synthesis. In hyperthyroidism patients, serum glucocorticoids while Type 1 AIT is treated with
thyroxine consummately de-escalated to nearly 25– thioamides. The effect of the glucocorticoids is twofold,
32% of baseline at one week after lithium management anti-inflammatory action and a decrement in the
and de-escalated to around 35% of baseline at 2 weeks peripheral transformation of T4 into T3. One can use
after treatment. Lithium is not the principal methylprednisolone at a dose of 20 – 40 mg / die or
management of hyperthyroidism because of its adverse dexamethasone at a dose of 3 – 6 mg / die, achieving
drug reactions and a narrow therapeutic range. euthyroidism generally within 1 – 3 weeks. Steroids are
However, it can be used to temporarily control gradually reduced and suspended only 2 – 3 months
hyperthyroidism in patients who cannot use thioamide after the start of the treatment in order to avoid possible
medications. Lithium can also be prescribed as an relapses [14, 17].
optional management in thyroid storm treatment. The
dose of lithium is 300–450 mg taken orally every 8
hours. Geriatric patients need a lower dose of lithium
to maintain the therapeutic degree because they have
de-escalated in total body water and GFR. Lithium is

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Oral cholecystography agents (sodium opiate and

sodium ipodate) have also been used for promptly
decreasing thyroid hormone degrees in combination
with MMI74 and perhaps helpful in thyroid storm. The
ubiquitous adverse drug reactions of cholestyramine are
bloating, flatulence, and constipation. Since
cholestyramine might attach to distinctive medications
bestowed concurrently, it is particularly recommended
that distinctive medications be received at least one hr
before or four to six hrs after cholestyramine.

Iodine-Containing Compounds
Figure 1: Mechanism of non-thioamide antithyroid drugs. Iodine- These are rarely used for the fast control of
containing compounds chiefly suppress thyroid hormone release hyperthyroidism in the context of thyroid storm or in
and transiently obviate organification. Lithium also suppresses the preoperative preparation for thyroid surgery. Iodine
thyroid hormone release and perhaps obviates thyroid hormone was used to treat hyperthyroidism before the discovery
secretion. Perchlorate suppresses active iodide intake by of thioamide antithyroid drugs. The iodine-containing
competitively attaching with NIS. Glucocorticoid suppresses
peripheral T4 to T3 conversion and perhaps obviates thyroid compounds used in the management of
hormone synthesis. MAbs act at the ectodomain of the TSH hyperthyroidism are KI in the form of potassium iodide
receptor while SMLs act at the transmembrane domain of the TSH tablets, a saturated solution of potassium iodide (SSKI),
receptor. MAbs: monoclonal antibodies; NIS: sodium iodide and Lugol’s solution. SSKI is prepared by adding KI
symporter; SMLs: small-molecule ligands; Tg: thyroglobulin; crystals to water until the saturation point of KI is
TSHR: thyroid stimulating hormone receptor.
reached. Lugol’s solution is an aqueous solution of
elemental iodine and KI. The preponderance actions of
Cholestyramine iodide on thyroid work suppression of thyroid hormone
Cholestyramine is an ionic exchange resin sequesters release from the thyroid gland and a transient de-
T4 in the intestine and escalates its fecal excretion. escalate in thyroid hormone secretion (the acute Wolff-
Both T3 and T4 are concentrated in the liver and Chaikoff effect). Iodide causes a transient de-escalate in
secreted in the bile in conjugated form and a small thyroid hormone generate and it also obviates
amount in unconjugated form. Free hormones are thyroglobulin proteolysis and release of T4 and T3.
released by bacterial enzyme deconjugation in the large Iodide used for management of thyroid storm and
intestine and reabsorbed to the blood circulation, preoperative preparation for emergency procedure.
completing the enterohepatic circulation of thyroid High-dose iodine in combination with distinctive
hormone. Experimentally, it has been revealed that 50 medications to manage thyroid storm can be used since
mg of cholestyramine can bind approximately 3000 lg iodide can quickly inhibit thyroid hormone release and
of T4 and thereupon can accelerate the clearance of thyroid hormone generation. The suggested dose of oral
thyroid hormones. Because of the escalated inorganic iodide for the treatment of thyroid storm is
enterohepatic circulation of thyroid hormones during 200–2000 mg per day. Used for potential treatment of
hyperthyroidism, attempts have been made to sequester Graves’ disease. Side effects of iodine-containing
these hormones in the intestine using ionic exchange compounds: Iodine has a few mild side effects such as
resins. Cholestyramine treatment has been surveyed in drug fever, sialoadenitis, conjunctivitis, mucositis,
the management of thyrotoxicosis as an adjunctive vasculitis, cutaneous rash, nausea, vomiting, diarrhea,
therapy to thioamides, and has been resulted to de- dysuria and only in rare cases, acute renal failure and
escalate thyroid hormone degrees promptly [20, 21]. thrombocytopenia and leukemoid eosinophilic
granulocytosis [17, 20].
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Conclusion pathophysiology and management of hyperthyroidism.

Hyperthyroidism is the consummate ubiquitous Conflict of Interest

antecedent of thyroid malfunction in areas with mild
and moderate iodine deficiency. Occurrences are seen at The author has no financial or proprietary interest in
all ages but presentation peaks between twenty and fifty any of material discussed in this article.
years of age secondary to the higher prevalence of
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