Hypothyroidism

Hypothyroidism – insufficient thyroid hormone action. More common in women, age > 65

Etiology

Normally, hypothalomus releases TRH Þ Pituitary releases TSH Þ thyroid releases T₄ and T₃ Þ act on thyroid receptors

abnormalities at any level can result in deficiency

(1) Primary Hypothyroidism – deficiency of thyroid itself – thyroid cannot respond to TSH

Destruction of Gland

Chronic autoimmune thyroiditis (Hashimoto’s) – antibody or cell-mediated cytotoxicity blocking TSH action

results in atrophic or goitrous thyroiditis
most common cause of primary hypothyroidism
associated with autoimmune disorders involving other endocrine glands (Addison’s, IDDM, rheumatoid)
autoantibodies against thryoglobulin and the enzyme thyroid peroxidase are common with this condition

Surgical removal – common therapy for many thyroid problems

Irradiation – therapeutic for thyrotoxicosis; or generalized irradiation for nonthyroid malignant disease

Inhibition of synthesis/release of T₄/T₃–iodine deficiency, Ý Ý iodide, anti-thyroid drugs, lithium, enzyme defects

Transient Hypothyroidism – following surgery or therapeutic radioactive iodine; also postpartum

(2) Secondary Hypothyroidism – deficient pituitary or hypothalamus – results in no TSH

(3) Peripheral Resistance to Thyroid Hormone – due to tissue-level receptor abnormalities

Pathophysiology

(1) Reduction of Oxidative Process and Thermogenesis – basal metabolic rate decreases substantially

the only tissues not affected by thyroid hormone are brain, spleen, lung, thymus, dermis, and reproductive organs

(2) Decreased Metabolic Activity – slowing of mentation, GI mobility, deep tendon reflex, drug metabolism, etc.

(3) Decreased adrenergic receptor sensitivity – ß chronotropic and inotropic effects in heart

Clinical Presentation

Characteristic Sign – myxedema – boggy non-pitting edema from Ý dermal accumulation of mucopolysaccharides and protein

often seen around eyes, pretibial area, dorsa of hands and feet, tongue, vocal cords (hoarse voice), supraclavicular fossa

Myxedemal Coma – in end-stage hypothyroidism; involves respiratory failure, decreased cardiac output, anemia, hypothermia, hypoglycemia, hyponatremia, and thyroid hormone deficiency

General – cold intolerance (due to ß skin blood flow), weight gain, fatigue, hypothermia, ß protein synthesis and catabolism, positive nitrogen balance

Skin –dry, yellow skin (Ý serum carotene from impaired conversion of Vit A), shallow pale complexion, coarse hair/alopecia

Respiratory – hoarse voice, sleep apnea

Cardiovascular – ß stroke volume and heart rate (no T₄/T₃ Þ inotropic and chronotropic effects), ß pulse pressure, Ý circulation time, ß ventricular performance (Ý afterload and change in myocardial Ca⁺⁺-dependent ATPase), Ý peripheral vascular resistance; ß tissue blood flow

Gastrointestinal – Hypomotility of the GI tract Þ constipation, anorexia; achlorhydria; ß B₁₂ absorption; antibodies against gastric parietal cells; ß glucose absorption

Neuromuscular – Pseudomyotonia (delayed relaxation phase of deep tendon reflexes), carpal tunnel syndrome, paresthesia, night blindness (retinene deficiency)

Musculoskeletal – ß rate of bone formation and resorption, linear growth deficiency Þ dwarfism, muscle stiffness and aching

Neuropsychic – mental slowness, slow speech, somnolence, lethargy

Congenital Hypothyroidism – most striking result is mental retardation since 80% of brain development is postnatal

T₄/T₃ Þ glial cell multiplication, myelinization, synaptic interconnections, dendritic arborizations

Labs – Ý serum Creatine Phosphokinase (CPK) ; Ý cholesterol (LDL) and triglycerides (VLDL); ß Na⁺; low-voltage EKG

Diagnosis

(1) Measure Free T₄ = (total T₄) x (RT₃U) – if T₄ is low, it is primary hypothyroidism only if [TSH] is high

(2) Measure TSH Only – common screening test since primary is much more common than secondary hypothyroidism

Other tests – TSH response to TRH administration, serum thyroid antibodies (esp. anti-microsomal or anti-peroxidase)

Thyroid Scan (gives a picture), Radioactive Iodide Uptake (gives a number)

Interpretation of Test Results:

	T₄	T₃RU	Free T₄ Index	TSH	Free T₄	RT₃	Response to TRH
primary hypohyroidism	ß	ß	ß	Ý	ß	ß	exaggerated
secondary hypothyroidism	ß	ß	ß	N or ß	ß	ß	absent or blunted
"euthyroid sick"*	ß	Ý or N	N or ß	N	Ý , N, ß	Ý	blunted or normal

*"euthyroid sick" – changes in thyroid function tests in NON-thyroidal illness

Treatment

Thyroid Hormone (Levothyroxine (T₄), since T₃ does not last as long) – also treat underlying disease