Thyroid disorders in high risk people:

Where to find and what should we do

during Covid 19 situation

Dr. Made Ratna Saraswati, SpPD-KEMD, FINASIM

Endocrinology and Metabolism Division, Department of Internal Medicine

Faculty of Medicine Udayana University, Sanglah Hospital Denpasar

Thyroid Webinar 4th September 2020

 Disclosure information

Made Ratna Saraswati

Endocrinology and Metabolism Division, Department of Internal Medicine
Faculty of Medicine Udayana University/Sanglah Hospital

has received honorarium as speaker from: PT. Merck Tbk Indonesia

 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

The hypothalamic-hypophysial-thyroidal
Fig.232 axis

TRH produces on the hypothalamus reachs

the thyrotrophs in the anterior pituitary by
the hypothalamic-hypophysial-portal system
and stimulates the synthesis and release of
TSH.

In both the hypothalamus and the pituitary, it

is primarily T3 that inhibits TRH and TSH
secretion respectively.
T4 undergoes monodeiodination to T3 in
neural and pituitary as well as in peripheral
tissues.

Greenspan’s Basic and Clinical Endrocrinology 8th ed. Lange, 2007. p. 221
Structure of thyroid hormone
 5’-monodeiodinase
T4 T3
(85%) • Hati
TRs
• Ginjal
T3 • otot skeletal TREs

TRs=thyroid hormone nuclear receptors .

TREs=thyroid hormone response elements
Regulation of thyroid hormone synthesis

Thyroid folilcles are formed by thyroid

epithelial cell surrounding proteinaceous
colloid, which contains thyroglobulin. Follicular
cells which are polarized, synthesize
thyroglobulin and carry out thyroid hormone
biosynthesis.

TSH-R = thyroid stimulating hormone receptor

Tg = thyroglobulin
NIS = sodium-iodide symporter,
TPO = thyroid peroxidase
DIT = diiodotyrosine
MIT = monoiodotyrosine

Harrison’s Principles of Internal Medicine, 17th ed. p. 2225

 Panel A, thyroid peroxidase (TPO)
glikoproten yang mengandung
heme, menempel pada membran
sel tiroid folikular pada sisi luminal
dari folikel tiroid.

Panel B, langkah pertama sintesis

tiroid melibatkan oksidasi enzim
yang dicetuskan oleh hidrogen
peroksida endogen.

Panel C, enzim yang sudah

teroksidasi bereaksi dengan iodide
yang terperangkap membentuk
“iodinating intermediate” (TPO–I
ox), yang belum sepenuhnya
dipahami. Beberapa peneliti
menyebut heme-linked iodinium
ion (TPO–I+), dan ada yang
menyebut hypoiodite (TPO–O–I¡).

Fig. A – C Synthesis of Thyroxine and Triiodothyronine Cooper DS, N Engl J Med 2005;352:905-17.
 Panel D, bila tidak ada obat antitiroid, “iodinating intermediate” bereaksi dengan residu tirosin spefisik pada
thyroglobulin (Tg) membentuk monoiodotyrosine (MIT) dan diiodotyrosine (DIT).
Subsequent coupling intramolecular MIT dan DIT membentuk T3 (triiodothyronine), dan coupling dua molekul
DIT membentuk T4 (thyroxine).

Fig. D Synthesis of Thyroxine and Triiodothyronine Cooper DS, N Engl J Med 2005;352:905-17.
 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

 Spectrum of thyroid disorder

• Thyroid dysfunction
• Hyperthyroidism and hypothyroidism

• Subclinical hyperthyroid and subclinical hypothyroidism

• Emergency in thyroid dysfunction: Thyroid Crisis (Thyroid storm), Coma Myxedema

• Thyroid nodule and cancer

• Thyroid autoimmunity
 Spectrum of thyroid disorder

• Thyroid dysfunction
• Hyperthyroidism and hypothyroidism

• Subclinical hyperthyroid and subclinical hypothyroidism

• Emergency in thyroid dysfunction: Thyroid Crisis (Thyroid storm), Coma Myxedema

• Thyroid nodule and cancer

• Thyroid autoimmunity
 INDICATIONS FOR TESTING
Increased or decreased metabolism (heat or cold intolerance, weight loss or gain, depression, anxiety, etc)
TSHs

Rendah Normal Tinggi

FT4

FT4 FT4

TSI (thyroid stimulating immunoglobulin), TPO ab (Thyroid Thyroid antibodies

peroxidase antibody), Trab (TSH receptor antibody) consist of :
Thyroid peroxidase and
thyroglobulin antibodies

Modified from: © 2006-2008

ARUP Laboratories.
All Rights Reserved.
Revised 1/10/08
Relationship between serum free thyroxine by dialysis (FT4) ng/dL and log10 TSH
in euthyroid, hyperthyroid, hypothyroid, and T4 supressed euthyroid

∆ Hypothyroid
(primary)

TSH µU/L
Euthyroid

Levothyroxine ○Hyperthyroid (nonpituitary)

suppressed (euthyroid )
FT4 (ng/dL)

Greenspan’s Basic and Clinical Endrocrinology 8th ed. Lange, 2007. p. 233
Relationship between serum free thyroxine by dialysis (FT4) ng/dL and log10 TSH
in euthyroid, hyperthyroid, hypothyroid, and T4 supressed euthyroid

Greenspan’s Basic and Clinical Endrocrinology 8th ed. Lange, 2007.

 Subclinical hypothyroidism and subclinical hyperthyroidism

• Dysfunction of the thyroid axis is common in the general population and even
more prevalent in the elderly, with an increased incidence of overt thyroid under-
or overactivity.

• This is augmented by significant numbers of patients with subclinical thyroid

pathology, which is found in more than 10% of patients aged over 80 years.

• The burden imposed by disorders of the thyroid in the elderly is, however,
unclear.

• Confounding factors include the ‘nonthyroidal illness syndrome’ or sick euthyroid

syndrome.

Boelaert K: Thyroid dysfunction in the elderly. Nat Rev Endocrinol 2013; 9: 194–204.
 ‘Nonthyroidal illness syndrome’
or sick euthyroid syndrome

The ‘nonthyroidal illness syndrome’, characterised by

• Decreased serum free triiodothyronine (T3)
• Low or normal TSH
• High reverse T3 and
• Relatively normal free thyroxine (T4) concentrations.

• It is important to make a differential diagnosis between this sick euthyroid syndrome and
subclinical hyperthyroidism.
• The failure of the serum tsh to rise in response to low circulating thyroid hormone
concentrations in critical illness arises from a degree of central hypothyroidism caused by
alterations in the set point of the hypothalamo-pituitary-thyroid axis.

Boelaert K: Thyroid dysfunction in the elderly. Nat Rev Endocrinol 2013; 9: 194–204.
 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

 Hyperthyroidism / Thyrotoxicosis

Hyperthyroidism
• refers to excess synthesis and secretion of thyroid hormones by
the thyroid gland, which results in accelerated metabolism in
peripheral tissues
Thyrotoxicosis
• Clinical syndrome that results when tissues are exposed to high
levels of circulating thyroid hormone.
 Table 1. Causes of Thyrotoxicosis
Thyrotoxicosis associated with a normal or elevated radioiodine uptake over the neck

• Graves’ Disease (GD)

• Toxic Adenoma (TA) or Toxic Multinodular Goiter (TMNG)
• Trophoblastic disease
• TSH-producing pituitary adenomas
• Resistance to thyroid hormone (T3 receptor mutation)
Thyrotoxicosis associated with a near-absent radioiodine uptake over the neck
• Painless (silent) thyroiditis
• Amiodarone-induced thyroiditis
• Subacute (granulomatous, de Quervain’s) thyroiditis
• Iatrogenic thyrotoxicosis
• Factitious ingestion of thyroid hormone
• Struma ovarii
• Acute thyroiditis
• Extensive metastases from follicular thyroid cancer

Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, Mcdougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan
MN.Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of The American Thyroid Association and American Association
of Clinical Endocrinologists. Hyperthyroidism Management Guidelines, Endocr Pract. 2011;17(3):e1-e65.
 Grave’s disease (diffuse toxic goiter)

The most common form of thyrotoxicosis

May occur at any age (peak 20 – 40 y.O.)
More commonly in female (5x)
Syndrome consist of one or more:
1. Thyrotoxicosis
2. Goiter
3. Ophthalmopathy (exophthalmus)
4. Dermopathy (pretibial myxedemia)
 Clinical features
• Common manifestation: palpitation, nervousness, easy fatigability, hyperkinesia,
diarrhea, excessive sweating, intolerance to heat and preference to cold.
• Marked weight loss without loss of appetite
• Thyroid enlargement
• Thyrotoxic eye signs
• Mild tachycardia
• Muscle weakness and loss of muscle mass
• Tremor
 Features of Grave’s disease

Opthalmopathy in Grave’s disease: lid retraction, Thyroid dermopathy Thyroid acropachy

periorbital edema, conjuctival injection and proptosis over the lateral aspect
of the shins

Harrison’s Principles of Internal Medicine, 17th ed. p. 2235 Harrison’s Principle

 Laboratory finding

• Elevated FT4 and suppressed TSH

• If eye sign are present, the diagnosis of grave’s disease can be made without
further test
• Thyroid antibody: tg ab and TPO ab, maybe present both in grave’s ds and
hashimoto’s thyroiditis
• TSH-R ab (stim) is specific for grave’s ds
• 123I or technecium scan is useful to evaluate the size, and the presence of hot /
cold nodules
• CT, MRI scan of the orbit
 Laboratory test useful in the differential diagnosis of hyperthyroidism

FT4 and TSH

FT4 ↑and TSH ↓ FT4 ↑and TSH ↑ FT4 N and TSH ↓

Hyperthyroidism TSH secreting - FT3

pituitary tumor
Eye signs No Eye signs No Eye signs GRTH
PRTH High Low
Goiter No Goiter Goiter

ESS
123I uptake Early Grave’s disease
Grave’s disease Drugs:
Toxic nodular goiter dopamine,
High Low corticosteroid

Grave’s disease Spontaneous resolving hyperthyroidism:

Toxic nodular goiter Subacute thyroiditis
Acute phase Hashimoto’s thyroiditis
Greenspan’s Basic and Clinical Grave’s disease or toxic nodular goiter in iodine loaded patient
Endrocrinology 8th ed. Lange, 2007. p. 226 Rare: Struma ovarii
 Treatment modalities for hyperthyroidism

• Beta-adrenergic blockade
should be given to elderly patients with symptomatic thyrotoxicosis and to other thyrotoxic
patients with resting heart rates in excess of 90 bpm or coexistent cardiovascular disease.

• Anti thyroid medication

• Iodine radioaktif (I131)
• Thyroidectomy
Chemical Structures of Propylthiouracil and Methimazole,
as Compared with Thiourea.

Cooper DS. N Engl J Med 2005;352:905-17.

 Panel D, bila tidak ada obat antitiroid,
“iodinating intermediate” bereaksi dengan
residu tirosin spefisik pada thyroglobulin (Tg)
membentuk monoiodotyrosine (MIT) dan
diiodotyrosine (DIT).
Subsequent coupling intramolecular MIT dan
DIT membentuk T3 (triiodothyronine), dan
coupling dua molekul DIT membentuk T4
(thyroxine).

Panel E, bila ada obat antitiroid (e.g.,

methimazole), obat menjadi substrat
alternative untuk “iodinating
intermediate”, berkompetisi untuk berikatan
dengan residu tirosin spefisik pada Tg
sehingga tidak terjadi sintesis hormon. Obat
intermediate dengan suatu ‘sulfur-linked
iodide’ secara teoritis adalah produk reaksi.

Pada Panel F, obat yang teroksidasi

membentuk obat disulfide yang tidak stabil,
mengalami degradasi spontan menjadi
molekul desulfurasi inaktif: methylimidazole.
Obat antitiroid mengganggu reaksi coupling
in vitro, namun belum jelas apakah hal ini
terjadi in vivo.

Fig. D – F Synthesis of Thyroxine and Triiodothyronine Cooper DS, N Engl J Med 2005;352:905-17.
Fig. Effects of Anti thyroid Drugs

The multiple effects of antithyroid drugs

include
inhibition of thyroid hormone synthesis and
a reduction in both intrathyroidal immune
dysregulation and (in the case of PTU) the
peripheral conversion of T4 toT3.

Tyrosine-Tg = tyrosine residues in thyroglobulin,

I+ = the iodinating intermediate
TPO = thyroid peroxidase.

Cooper DS. N Engl J Med 2005;352:905-17.

Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018 European Thyroid Association Guideline for the Management of
Graves’ Hyperthyroidism. Eur Thyroid 2018;7:167-186.
 Biochemistry Serology Thyroid imaging

Figure. Algorithm for investigating a patient with suspected Graves’ hyperthyroidism

Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018 European Thyroid Association Guideline for the Management of
Graves’ Hyperthyroidism. Eur Thyroid 2018;7:167-186.
 Persistent
Untreated GD Hyperthyroidism Relapse

MMI Long-term
MMI (CBZ) low-dose
Adults : 18 months for further
Children: 36 months 12 months MMI

Figure. Algorithm for management of a patient with Graves’ hyperthyroidism

GD=Graves’ disease, MMI=methimazole, CBZ=carbimazole, GO=Graves’ orbitopathy, RAI=radioactive iodine, Tx=Total thyroidectomy
Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018 European Thyroid Association Guideline for the Management of
Graves’ Hyperthyroidism. Eur Thyroid 2018;7:167-186.
 Table 1. Mechanism of action of
thyroid drugs
• Intrathyroidal inhibition of:
• Iodine oxidation/organification
• Iodothyrosine coupling
• Follicular cell growth
• Extrathyroidal inhibition of T4/T3 conversion
(PTU)
Chemical structures of commonly used
antithyroid drugs

Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018 European Thyroid Association Guideline for the Management of
Graves’ Hyperthyroidism. Eur Thyroid 2018;7:167-186.
Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018
European Thyroid Association Guideline for the Management of
Graves’ Hyperthyroidism. Eur Thyroid 2018;7:167-186
Nakamura H et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease.
J Clin Endocrinol Metab 2007 Jun; 92:2157-62
Fig. Comparison of the efficiency of treatment with MMI 30mg/d and PTU 300mg/d or MMI 15mg/d
in patients with GD in terms of normalizing serum FT4 levels [<1.7 ng/dl (21.9 pmol/liter)]

Nakamura H et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease.
J Clin Endocrinol Metab 2007 Jun; 92:2157-62
Methimazole vs. Propylthiouracil for Hyperthyroidism
Allan S. Brett, MD reviewing Nakamura H et al. J Clin Endocrinol Metab 2007 Jun
Available from: https://www.jwatch.org/jw200706190000001/2007/06/19/methimazole-vs-propylthiouracil-hyperthyroidism

Methimazole was superior overall, and lower doses seemed sufficient for patients with mild-to-moderate hyperthyroidism.

Both methimazole and propylthiouracil (PTU) are used to treat hyperthyroidism. To compare these drugs, Japanese researchers randomized 396 patients
with Graves hyperthyroidism to receive 15 mg of methimazole once daily, 30 mg of methimazole daily (given as 15 mg twice daily), or 100 mg of PTU three
times daily.

At each of three time points (4, 8, and 12 weeks), the proportion of patients with normalized free thyroxine (T4) levels was higher in the 30-mg methimazole
group than in the other two groups. The differences were of borderline statistical significance at 4 and 8 weeks but significant at 12 weeks (normal free T4
achieved in 97%, 86%, and 78% of patients in the 30-mg methimazole, 15-mg methimazole, and PTU groups, respectively). In patients with mild or moderate
hyperthyroidism, normal free T4 was achieved at similar rates in the three groups. However, in patients with severe hyperthyroidism (i.e., free T4 ≥7 ng/dL),
higher-dose methimazole was more effective than lower-dose methimazole or PTU. Transaminase elevations and leukopenia occurred less commonly with
both doses of methimazole than with PTU. Rash was less common with lower-dose methimazole than with higher-dose methimazole or PTU.

Comment:
Based on these results, the authors favor methimazole — at doses of 15 mg/day for those with mild-to-moderate
hyperthyroidism, and 30 mg/day for those with severe hyperthyroidism.
Because other studies have reached similar conclusions, most U.S. experts already favor methimazole.
One exception is that PTU is recommended during pregnancy.

Nakamura H et al. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves’ disease.
J Clin Endocrinol Metab 2007 Jun; 92:2157-62
 Table 2. Adverse events of antithyroid drugs
Common (1.0 – 5.0%) Skin rash
Urticaria
Arthralgia, polyarthritis
Fever
Transient mild leukopenia
Rare (0.2 – 1.0%) Gastrointestinal
Abnormalitas of taste and smell
Agranulocytosis
Very rare (<0.1%) Aplastic anemia (PTU, CBZ)
Thrombocytopenia (PTU, CBS)
Vasculitis, lupus-like, ANCA + (PTU)
Hepatitis (PTU)
Hypoglycemia (anti-insulin Abs; PTU)
Cholestatic jaundice (CBS/MMI)
PTU=propylthiouracil, MMI=methimazole, CBZ=carbimazole, ANCA=antineutrophil cytoplasmic antibody
Kahaly GJ, Bartalena L, Hegedus L, Leenhardt L, Poppe K, Perace SH. 2018 European Thyroid Association Guideline for the Management of Graves’
Hyperthyroidism. Eur Thyroid 2018;7:167-186.
 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

 Hypothyroidism

• Clinical syndrome resulting from a deficiency of thyroid hormone, which is in

turn results in a generalized slowing down of metabolic processes.
• The most common disorders of thyroid function
• Most often caused by a disorder of the thyroid gland that leads to a decrease in
thyroidal production and secretion of T4 (thyroxin) and T3 (triiodothyronine)
(in which case it is referred to as primary hypothryoidism)
 Pathogenesis of hypothyroidism

• Thyroid hormone deficiency affects every tissue – the symptoms are

multiple.
• Characteristic finding: the accumulation of glycosaminoglycans –
mostly hyaluronic acid – in interstitial tissues (skin, heart muscle, and
striated muscle) with increased of capillary permeability to albumin
account for interstitial edema.
This is due to decreased destruction
(not excessive production of glycosaminoglycan.
 Causes of hypothyrodism

• Primary hypothyroidism (thyroid failure)

• Central hypothyroidism
• Secondary (to pituitary TSH deficit)
• i.e. Pituitary adenoma, pituitary ablative therapy, pituitary destruction
• Tertiary (due to hypothalamic deficiency of TRH) - rare

• Peripheral resistance to the action of thyroid hormones

• Transient hypothyroidism
 Primary hypothyrodism
• Thyroid dysgenesis
• Destruction of thyroid tissue
• Chronic autoimmune thyroiditis (atrophic and goitrous forms)
• Radiation : 131I therapy for thyrotoxicosis
External radiotherapy to the head and neck for nonthyroid malignant disease
• Subtotal and total thyroidectomy
• Infiltrative disease of the thyroid (amyloidosis, scleroderma)
• Defective thyroid hormone biosynthesis
• Iodine deficiency
• Drugs with antithyroid actions: lithium, iodine, and iodine-containing drups and radiographic
contrast agents

Bravermen LE & cooper DS. Introduction to hypothyroidism. In: bravermen LE & cooper DS (editors). Werner & ingbar’s the thyroid: a
fundamental and clinical text. 10th edition. Philadelphia: lippincott william & wilkins, 2013. P. 523-4.
 Signs and symptoms of hypothyroidism in adults
Signs and symptoms of hypothyroidism tend to be
more subtle than those of hyperthyroidism
• Dry skin
• Cold sensitivity
• Fatigue
• Muscle cramps
• Voice changes
• Constipation are among the most common. Fig. Facial appearance in hypothyroidism
Note: puffy face, puffy eyes and thickened, pale skin

Harrison’s Principles of Internal Medicine, 17th ed. p. 2231

 Less common symptoms of hypothyrodism

Typically associated with severe hypothyroidism

• Carpal tunnel syndrome
• Sleep apnea
• Pituitary hyperplasia that can occur with or without hyperprolactinemia and
galactorrhea, and hyponatremia that can occur within several weeks of the
onset of profound hypothyroidism.
• Ankle reflex relaxation time, a measure rarely used in current clinical practice
today
 Diagnosis
• Primary hypothyroidism
• Low serum FT4 or FT4I, elevated serum TSH
• Serum T3 variable, maybe normal
• Thyroid autoantibodies (hashimoto’s thyroiditis)
• Secondary
• Low serum FT4 or FT4I, but serum TSH not elevated
• Absence TSH response to TRH (partial or intact response indicates pituitary deficiency)

Further test and assessment (imaging)

• Assessment of thyroid iodine metabolism and biosynthetic activity
• Thyroid imaging
• Radionucleid imaging
• Thyroid ultrasonography
• Thyroid biopsy
 When to treat hypothyroidism

• General agreement that patients with primary hypothyroidism with TSH levels
above 10 miu/L should be treated
• Patients with TSH levels of 4.5–10 miu/L will benefit is less certain.
• There are virtually no clinical outcome data to support treating patients with
subclinical hypothyroidism with TSH levels between 2.5 and 4.5 miu/L.
• The possible exception to this statement is pregnancy because the rate of
pregnancy loss, including spontaneous miscarriage before 20 weeks gestation
and stillbirth after 20 weeks, have been reported to be increased in anti-thyroid
antibody–negative women with tsh values between 2.5 and 5.0.

Garger et al. Clinical practice guideline for hypothyroidsm in adults. Thyroid 2012; 22 (12)
 L-thyroxine treatment of hypothyroidism
• Conversion of T4 to T3 was documented in 1970

• L-thyroxine monotherapy has become the mainstay of treating

hypothyroidism, replacing desiccated thyroid and other forms of l-thyroxine
and l-triiodothyronine combination therapy.

• A number of studies, following a 1999 report citing the benefit of l-thyroxine

and l-triiodothyronine combination therapy, have re-addressed the benefits
of synthetic l-thyroxine and l-triiodothyronine combination therapy but have
largely failed to confirm an advantage of this approach to improve cognitive
or mood outcomes in hypothyroid individuals treated with lthyroxine alone.
Levothyroxin has a narrow therapeutic index,
both underdosage (subclinical hypothyroidism)
and excessive dosage (subclinical
hyperthyroidism) are associated with adverse
symptoms.
The consequent necessity for careful titration of
doses has had an impact on the issue of
switchability or bioequivalence.
 Monitoring of treament

Normalization of a variety of clinical and metabolic end points

are further confirmatory findings that patients have been
restored to a euthyroid state, including:
• Resting heart rate
• Serum cholesterol
• Anxiety level
• Sleep pattern
• Menstrual cycle abnormalities including menometrorrhagia
 Therapeutic endpoints
In the treatment of primary hypothyroidism

• The most reliable therapeutic endpoint for the treatment of primary

hypothyroidism is the serum TSH value.
• Confirmatory total T4, free T4, and T3 levels do not have sufficient specificity to
serve as therapeutic endpoints by themselves, nor do clinical criteria. Moreover,
when serum TSH is within the normal range, free T4 will also be in the normal
range.
• On the other hand, T3 levels may be in the lower reference range and
occasionally mildly subnormal.
 Monitoring of treament

Q Which is the best indicator for euthyroid in hypothyroid replacement?

Normal metabolic state has been attained is normalization of the TSH level down to the rage of 0,5-1.5 mU/L.
On average, this will equate to an ultimate full replacement dose of ~1.7 µg/kg/day.
Patients who have had a total thyroidectomy for example for thyroid malignancy, especially when surgery
was followed by radioiodine ablation, will have no residual thyroid tissue and their requirement will be
closer to 2.1µg/kd/day.
In patients taking thyroxine, measure serum T3 levels may be a better indicator of the metabolic state than
serum T4 levels but dosage adjusments are best determined by clinical criteria and TSH.
However, in patients with pituitary or hypothalamic disease in whom it is not feasible to monitor TSH as an
indicator of dosage adequacy, measurement of serum fT4 and and T3 are generally adequate to monitor
dosage.
Complication of untreated hypothyroidism

• Myxedema coma
• Myxedema and heart disease
• Hypothyroidism and neuropsychiatric disease
Measurement of serum TSH is the primary screening test:
• For thyroid dysfunction
• For evaluation of thyroid hormone replacement in patients with primary
hypothyroidism
• For assessment of suppressive therapy in patients with follicular cell–derived
thyroid cancer.
Pitfalls encountered
when interpreting serum TSH level

• TSH tend to be lowest in the late afternoon and highest around the hour of sleep.
• In light of this, variations of serum TSH values within the normal range of up to 40%–50% do
not necessarily reflect a change in thyroid status.

Garger et al. Clinical practice guideline for hypothyroidsm in adults. Thyroid 2012; 22 (12)
 Point of view

▪ Physiology of thyroid gland

▪ Spectrum of thyroid disorder

▪ Hyperthyroidism

▪ Hypothyroidism

▪ Covid 19 and thyroid disorders

• Are people with autoimmune thyroid disease, such as hashimoto’s thyroiditis or graves’ disease, at more risk
for acquiring covid-19 or having a more serious covid-19 infection?
• Are there any shortages of levothyroxine?
• How do patients taking methimazole for hyperthyroidism tell the difference between a covid-19 infection or
side effects of methimazole?
• How can methimazole be given to patients with critical illness?
• Is it safe to delay a biopsy of my thyroid nodule?
• Are people with thyroid cancer at more risk from covid-19 because they are immunocompromised?
• Is it safe to delay thyroid surgery because of the covid 19 pandemic
• Is it safe to delay radioactive iodine treatment because of the current covid-19 pandemic?
Available from: https://www.thyroid.org/covid-19/coronavirus-frequently-asked-questions. Downloaded 2 September 2020.
 Hashimoto’s thyroiditis and Grave’s disease

Q Are people with autoimmune thyroid disease, such as hashimoto’s

thyroiditis or graves’ disease, at more risk for acquiring COVID-19 or
having a more serious COVID-19 infection?

• The u.S. Centers for disease control (CDC) advises that people who are immunocompromised are at
higher-risk of severe illness from COVID-19. Immunocompromised people have a weaker immune
system and have a harder time fighting infections. However, the immune system is complex, and
having autoimmune thyroid disease does not mean that a person is immunocompromised or will be
unable to fight off a viral infection.
• Thus far, there is no indication that patients with autoimmune thyroid disease are at greater risk of
getting covid-19 or of being more severely affected should they acquire the covid-19 infection.
• Everyone should continue to practice the recommended hand hygiene and social distancing
recommendations to avoid covid-19 infection.
 Hyperthyroidism
How do patients taking methimazole for hyperthyroidism tell the
Q difference between a COVID-19 infection or side effects of
methimazole?

• Many patients with graves’ disease and other types of hyperthyroidism are treated with the medication known as
methimazole (or a similar medication called propylthiouracil [PTU]). A rare side effect of these antithyroid medications is a
condition called agranulocytosis (occurring in 0.2-0.5% of people taking the medication), in which the number of the
immune cells that fight infection decrease. Patients may have symptoms such as fever or sore throat. If these occur,
patients are often told to stop the methimazole and go to a laboratory to have blood testing done.
• As fever and signs of illness can also overlap with the symptoms of covid-19 infection, many patients who happen to also
be taking methimazole may be concerned that they have become infected with covid-19. Should they quarantine at home if
they have some of these symptoms?
• Because agranulocytosis with fever can represent a serious infection, the possibility should not be ignored.
Agranulocytosis is less common in patients who have been taking methimazole for a long time or when the dose of the
medication is low (e.g. 15 mg in one study), but it can still occur. If a fever or other symptoms of an infection start while
taking methimazole, it is best to contact your endocrinologist or other provider to determine how best to be evaluated.
• Patients should always seek medical attention for symptoms that seem urgent or life-threatening. Any patient with new
fever, cough, or other typical symptoms of COVID-19 infection should seek medical attention immediately, regardless of
methimazole use.
 Hyperthyroidism
Q How can methimazole be given to patients with critical illness?

• Methimazole is an oral medication and stopping these medications can lead to worsening of hyperthyroidism. During a
critical respiratory illness, especially when a ventilator (breathing machine) is required, a patient may not be able to take
medications by mouth. When treatment of hyperthyroidism is necessary, different routes for giving methimazole may be
used. Providers taking care of patients with critical illnesses will be able to determine the best approach for making sure
that a patient with hyperthyroidism continues to receive treatment as needed.
• The placement of a naso-gastric tube or a dobhoff tube allows the same methimazole pill to be delivered to the gut
(digestive system) in a patient who is unable to swallow.
• If the enteric route (through the stomach) is not available, these medications can be prepared for intravenous (iv) use: IV
methimazole has been given by adding 500mg of methimazole powder to 0.9% sodium chloride solution to a final volume
of 50ml and administering the correct dose as a slow IV push over 2 minutes.
• PTU is relatively insoluble. An IV formulation used in one report was made by dissolving tablets in isotonic saline with an
alkaline ph (ph 9.25).
• Enema or suppository formulations have also been used and require specific preparation.
 Summary

• In general, TSHs is an important early test for thyroid function

• In abnormal result of TSHs, the next laboratory examination is FT4, in certain condition also FT3

• Treatment of choice in hyperthyroidism is anti thyroid drug, radioactive iodine (i131), or thyroidectomy.
Treatment of choice is anti thyroid drug methimazole. Stopping these medications can lead to
worsening of hyperthyroidism
• Treatment for hypothyroidism is levothyroxine. Levothyroxin is consider to have narrow therapeutic
index. The consequent necessity for careful titration of doses has had an impact on the issue of
switchability or bioequivalence.
• Certain cases such as subclinical hypothyroidism or subclinical hyperthyroidism, clinical consideration
should be taken whether patients need to be treated
Thank you