Thyroid disorders –
Concerning the excess production & release of hormone, Associated with hormone deficiency, Inflammations, The formation of nodules or lumps/ benign lesions, Malignant lesions.
Hyperthyroidism/ Thyrotoxicosis
Causes of hyperthyroidism
Primary :
Diffuse toxic hyperplasia (Graves disease)
Hyperfunctioning toxic MNG
Hyperfunctioning toxic adenoma
Hyperfunctioning carcinoma
Iodine induced
Neonatal Tx assoc with Maternal Graves
Secondary : TSH-secreting pituitary adenoma
OTHERS: Subacute granulomatous thyroiditis, Hashimoto’s thyroiditis, Struma ovarii
Clinical features
Hypermetabolic state – increased BMR, heat intolerance (sweating), wt loss despite increased appetite
Skin soft, warm, flushed, increased heat loss, increased blood flow – peripheral vasodilation.
CVS – Increased cardiac output, due to increased contractility & peripheral O2 requirement. Tachycardia, arrhythmias, palpitations, cardiomegaly, congestive cardiac failure, cardiomyopathy.
Neuromuscular – overactivity of sympathetic nervous system, tremor, hyperactivity, emotion, anxiety, inability to concentrate, insomnia, proximal muscle weakness due to loss of muscle mass.
Ocular changes – staring gaze, lid lag
GI – hyperstimulation of gut – hypermotility, malabsorption, diarrhoea.
MSK – Thyroid hormone stimulates bone resorption – osteoporosis, risk of fractures.
Hepatomegaly – fatty change in hepatocytes.
Thyroid storm – abrupt onset, febrile, arrhythmias.
Hair loss, oliomenorrhoea.
Graves disease
Graves’ disease / Parry’s or Basedow’s disease or diffuse toxic goiter, is a disorder with three major manifestations: 1. hyperthyroidism with diffuse goiter, 2. ophthalmopathy, 3. dermopathy.
They do not appear together. Indeed, one or two need never appear, and moreover, the three may run courses that are largely independent of one another.
Prevalence : Most common form of thyrotoxicosis. 2% of the female population. Females 7:1. Peak incidence between the third and fourth decades and the reason for the female predominance in this as in all thyroid diseases is unknown. Genetic factors play an important role – increased frequency haplotypes HLA-B8 and -DRw3 in Caucasian, HLA-Bw36 in Japanese, and HLA-Bw46 in Chinese patients with the disease.
Etiopathogenesis : Autoimmune disorder; Auto Antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin.; Antibody to Thyroid stimulating Immunoglobulin (LATS); TSH binding inhibitor Ig.
Clinical features
Common : palpitations, nervousness, easy fatigability, hyperkinesia, tremors, diarrhea, excessive sweating, intolerance to heat, preference for cold. Marked weight loss without loss of appetite. Proximal muscle weakness and loss of muscle mass. Thyroid gland diffused enlarged – asymmetric or lobular. Dermopathy – thickening of skin, particularly over the lower tibia. The skin cannot be picked between the fingers. Separation of the fingernails from their beds – onycholysis.
The eye signs : The spastic signs : The stare, lid lag, and lid retraction and accounts for the “frightened” facies. ; The mechanical signs : proptosis with congestive oculopathy characterized by conjunctivitis, periorbital swelling, and the potential complications of corneal ulceration, optic neuritis, and optic atrophy.
Exophthalmos may be unilateral early but usually progresses to bilateral involvement.
Pathology :
The thyroid gland is diffused enlarged, hypercellular, soft and vascular. There is a parenchymatous hypertrophy and hyperplasia. Usually there is little or no colloid present with mild lymphocytic infiltration. The disease is associated with generalized lymphoid hyperplasia and infiltration and occasionally with enlargement of the spleen and thymus.
Associated Pathology –
Degeneration of skeletal muscle fibers, enlargement of the heart, fatty infiltration or diffuse fibrosis of the liver, decalcification o the skeleton, and loss of body tissue. Inflammatory infiltrate of the orbital contents. Thickening of the dermis, which is infiltrated with lymphocytes.
Multinodular Goitre
Toxic nodular goiter (TNG) – 2nd most common cause of hyperthyroidism after Graves disease (15-30%). In areas of endemic iodine deficiency, it ranks first. More common in women than in men. Originally described by Henry Plummer in 1913, also known as Plummer disease.
Pathophysiology –
Spectrum ranging from a single hyperfunctioning nodule within a thyroid that contains other nonfunctioning nodules to multiple areas of hyperfunction throughout the gland. Variable growth of individual nodules, non encapsulated,with some resulting in hemorrhage and degeneration, followed by healing with fibrosis. Subsequently calcification. Autonomously functioning nodules may become toxic in 10% of patients. Signs and symptoms similar to other types of hyperthyroidism.
Obstructive symptoms –
A significantly enlarged goiter can cause symptoms related to mechanical obstruction. A large substernal goiter may cause dysphagia, dyspnea, or frank stridor. Rarely, this may result in a surgical emergency. Involvement of the recurrent or superior laryngeal nerve may result in complaints of hoarseness or voice change. Mechanical obstruction may result in superior vena cava syndrome, with engorgement of facial and neck veins (ie, Pemberton sign).
Pathology –
The histologic appearance – range from the presence of normal-sized follicles, microfollicles, or macrofollicles all coexisting within the same gland. Early goiters display micronodular growth patterns. Actively proliferating follicular cells can be observed within some thyroid follicles, resulting in budding intraluminal projections. Areas of hemorrhage with calcification.
Diffuse goitre – simple/ toxic
Simple – colloid – diffusely enlarged without nodularity, enlarged follicles filled with colloid.
Endemic – Iodine deficiency, goitrogens – Increased calcium, brassica/ cruciferae ( cabbage, cauliflower,turnips, cassava, brussel sprouts).
Sporadic – Young adult females, hereditary enzymatic defects.
Generally euthyroid, sometimes TSH high.
Hypothyroidism
Hypothyroidism results from failure to maintain adequate tissue levels of thyroid hormone. 15 per 1000 in females and 1 per 1000 in males, peak in the fifth or sixth decades.
Primary hypothyroidism (failure of the thyroid gland to produce hormones);
Secondary hypothyroidism (the thyroid gland is normal and the pituitary fails to secrete adequate TSH;
Tertiary hypothyroidism (failure to secrete thyrotropin releasing-hormone [TRH]).
Etiology
Primary – Developmental – dysgenesis, TSH receptor mutations; Post ablative – surgery, radioiodine therapy, external radiation; Autoimmune; Iodine deficiency; Drugs – lithium, p-amino salicylic acid; Dyshormonogenetic goitre (congenital biosynth defect)
Secondary – pituitary failure
Tertiary – Hypothalamic failure
Epidemiology – White females, ranging from 4:1 to 19:1 over males. The frequency increases with age. Hypothyroidism is most prevalent in elderly populations and develops with increasing age.
Cretinism
Hypothyroid in infancy/ childhood. French chretein, Christ-like. Endemic dietary Iodine deficiency – Himalayas, Inland China, Africa. Impaired devpt of skeletal system, CNS, MR, short stature, protruding tongue, umbilical hernia.
Congenital hypothyroid
Relatively common disorder, 1 per 4000 newborns. Absence of hormone in adequate amounts during 1st 2 yrs (brain devpt) causes permanent brain damage. As thyroid hormone is necessary for linear growth, severe growth retardation occurs if it is absent during childhood. If treatment is started while the epiphyses are open and undamaged, growth will resume. In addition to the above problems, these patients may have all the other signs and symptoms of hypothyroidism.
Clinical features – Severely retarded and cannot communicate. Short stature, epiphyses are still open, although severely damaged. Thick, dry skin. Thick tongue, saddle nose. Primary teeth still prsent; the secondary teeth have not erupted.
Hypothyroidism
Symptoms – Fatigue, lethargy; Weight gain; Decreased appetite; Constipation; Cold intolerance; Dry skin; Sleepiness; Muscle pain, joint pain, weakness in extremities; Depression; mental impairment; orgetfulness, inability to concentrate; Menstrual disturbance, impaired fertility; Decreased perspiration; Paraesthesia ; Blurred vision
Signs – Jaundice; Pallor; Coarse, brittle, strawlike hair; Loss of scalp hair, axillary hair, pubic hair, or a combination; Dull facial expression; Periorbital puffiness; Macroglossia; Goitre; Hoarseness; Decreased systolic & increased diastolic BP; Bradycardia; Pericardial effusion; Nonpitting edema (myxedema); Pitting edema of lower extremities
Myxoedema
Both hypothyroid and hyperthyroid conditions, due to the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis, results in thickening of the skin and subcutaneous tissues. Mechanism is still not yet understood – thyroid hormones affect the synthesis and catabolism of mucopolysaccharides and collagen by dermal fibroblasts. The fibroblasts in pretibial dermis accumulate by autoimmune process that causes Grave’s disease. Systemic or topical glucocorticoids, high-dose intravenous immunoglobulin, along with correction of the original hyperthyroidism/hypothyroidism.
Myxoedema coma
Severe form of hypothyroidism that results in an altered mental status, hypothermia, bradycardia & hyponatremia. Cardiomegaly, pericardial effusion, and ascites. Most commonly occurs in individuals with undiagnosed or untreated hypothyroid who are subjected to an external stress such as cold exposure, surgery, infection.
Hashimoto’s thyroiditis
Hashimoto thyroiditis is part of the spectrum of autoimmune thyroid diseases (AITD). First described by Hakaru Hashimoto, a Japanese surgeon working in Berlin, Germany (struma lymphomatosa). Patients have antibodies to various thyroid antigens, which include antithyroid peroxidase (anti-TPO) & antithyroglobulin (anti-Tg).
Pathophysiology –
Destruction of the thyroid cells by various cell- and antibody-mediated immune processes. Antibodies binding to and blocking the thyroid-stimulating hormone (TSH) receptor, so impairment in thyroid function. The result is inadequate thyroid hormone production and secretion. The thyroid gland is typically goitrous but may be atrophic or normal in size.
Epidemiology – Females, 30-50 years.
Pathology –
Enlarged thyroid, c/s yellow-tan, firm, nodular. Atrophic follicles, infiltration of lymphocytes with germinal follicles. Some follicles lined by Hurthle cells, with eosinophilic granular cytoplasm. High risk for DM, SLE, NHL.
De Quervian Thyroiditis
A viral infection or a postviral inflammatory response, coxsackievirus, mumps, measles, adenovirus, & influenza. A strong association exists with HLA-B35. Viral infection provides an antigen, binds to molecules on macrophages. This complex activates cytotoxic T lymphocytes that damage thyroid follicular cells. Destruction of follicular epithelium. Thyroid hormones are released into the blood, elevation of T3 & T4 and suppress TSH secretion.
Epidemiology – Females, 30-50 years Benign self-limited disease. Pain, Mild and transient hyperthyroidism occurs, and, in 50% of patients, hypothyroidism may occur later.
Clinical features
Pain, gradual or sudden onset; involves both lobes; radiates to the neck,; Dysphagia, Hoarseness. Constitutional symptoms – Fever, Malaise, Anorexia, Fatigue, Muscle aches.
Symptoms of hyperthyroidism (palpitations, tremulousness, heat intolerance, sweating, nervousness) occurring in the initial phase of the disease. Hyperthyroidism is mild, transient symptoms, usually lasting 3-6 weeks. Symptoms of hypothyroidism, occurring in the late phase of the disease in as many as half the cases.
Pathology –
Unilateral/ bilateral enlarged, firm, rubbery, yellow-white, adherent to surrounding areas. Chronic inflammation with lymphocytes, histiocytes, plasma cells, multinucleate giant cells. Extensive fibrosis.
Other Thyroiditis :
Subacute lymphocytic thyroiditis – Silent/ painless, Post partum, middle aged adults, similar to Hashimoto’s, but no Hurthle cells.
Riedel’s thyroiditis – hard, fixed mass, extensive fibrosis.
Palpation thyroiditis – Vigorous clinical palpation. Follicular disruption with inflammation.
References :
Pathologic Basis of disease – Robbins & Cotran, 7th Ed; Principles of Internal Medicine – Harrisons, 15th Ed; Surgical Pathology – Ackerman, 9th Ed; Textbook of Medical Physiology – Guyton, 9th Ed; Lecture notes on Pathology – Cotton, 4th Ed, Aids to Pathology – Dixon/ Quirke 4th Ed.
Clinical Pathology 
