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Pseudohypoparathyroidism (PHP) is a genetic disorder of end-organ insensitivity to the effect of PTH, which results in hypocalcemia, hyperphosphatemia, and increased PTH levels

Symptoms & Signs 

-As the name implies, patients with pseudohypoparathyroidism have signs and symptoms characteristic of hypoparathyroidism

-PHP may be associated by a characteristic phenotype known as Albright Hereditary Osteodystrophy (AHO) which includes short stature, round facies, shortening of the fourth metacarpals (brachydactyly), and osteoma cutis 

-Examination of the clenched fist reveals a characteristic depression where the knuckle of the fourth metacarpal should be located.

Diagnosis 

-A high concentration of serum PTH, low serum calcium, high phosphate, and 

signs and symptoms of hypoparathyroidism

-patients with pseudohypoparathyroidism do not respond to infused PTH

Treatment 

Treatment is the same as for hypoparathyroidism

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Introduction 

-The four parathyroid glands produce and secrete PTH

-Hypoparathyroidism develops when the parathyroid glands fail to secrete sufficient quantities of PTH, resulting in a low calcium level and a high phosphorus level 

-The most common cause of hypoparathyroidism is neck surgery with removal or destruction of the parathyroid glands

-Other causes include congenital abnormalities of the third and fourth pharyngeal pouches (DiGeorge syndrome), autoimmune or drug induced or radiation induced hypothyroidism 

Symptoms & Signs 

Skin: Dry, scaly skin, coarse hair

Ocular: Cataracts, Papilledema 

Dental: enamel hypoplasia, defective root formation, delayed teeth eruption

Respiratory: Bronchospasm, laryngospasm, stridor 

Cardiac: Heart failure, Prolonged QT interval on ECG

Psychological: Confusion, behavioral changes, psychosis 

Neuromuscular: numbness, tingling, carpopedal spasms, seizures, Parkinsonism

Tetany: Spontaneous tonic muscular contractions; Classically diagnosed by Chvostek sign and Trousseau sign

Chvostek sign: twitching or contraction of the facial muscles in response to tapping the facial nerve at a point anterior to the ear and above the zygomatic bone

Trousseau sign: it is elicited by inflating the sphygmomanometer with the cuff around the arm above the systolic blood pressure for 3 min; The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct

Diagnosis 

Labs: Inappropriately low or undetectable PTH level, low calcium level, high phosphorus level

EKG: a prolonged QT interval on the ECG

Treatment 

Recombinant PTH; IV or oral calcium, Vitamin D supplementation; correction of hypomagnesemia 

Thyroid cancer is the most common malignancy of the endocrine system

-Most thyroid cancers occur in the young with only one-third of cases occurring after age 55

-Thyroid cancer can be of follicular cell origin or C-cell origin or lymphoid origin. 

Originating from follicular cells 

Papillary 80% 

Follicular 11% 

Hürthle cell 3% 

Anaplastic 2% 

Originating from C-cells or parafollicular cells 

Medullary 4%

Originating from lymphoid cells 

Thyroid lymphoma 1% 

Most of these carcinomas are treated by surgery, radioiodine, and levothyroxine to suppress TSH

Introduction 

Toxic multinodular goiter refers to autonomous hyperfunctioning thyroid nodules that produce hyperthyroidism 

-it is more common in women over the age of 60 and in iodine-deficient regions

-it is the second most common cause of hyperthyroidism after Graves disease 

Symptoms & Signs 

Symptoms and signs of hyperthyroidism are similar to Graves’ disease: weight loss, nervousness, weakness, tremors, sweats, tachycardia, heart failure, arrhythmias, atrial fibrillation, congestive heart failure 

Physical examination reveals a multinodular goiter which may extend substernally

Diagnosis 

Labs: low or undetectable TSH, elevation in serum serum T3 levels, with less striking elevation of serum T4

Radioiodine scan: multiple functioning nodules in the gland with iodine localized to active nodules

Treatment 

methimazole (preferable) or propylthiouracil followed by subtotal thyroidectomy; RAI therapy 

Introduction 

-Thyroid nodules is the most common endocrinopathy 

-They are extremely common, particularly among women

– About 90% of palpable thyroid nodules are benign adenomas, colloid nodules, or cysts, but some are malignancies 

-Most patients with a thyroid nodule are euthyroid, but some are hypothyroid or hyperthyroid 

-The most common neoplasm is the follicular adenoma (benign thyroid nodule) 

– A thyroid nodule is more likely to be a cancer in a man than in a woman and in young patients (under 20 years) and older patients (over 60 years)

Symptoms & Signs 

-Thyroid nodules usually are asymptomatic

-neck discomfort, dysphagia, choking sensation, hoarseness

-Large substernal goiters can cause superior vena cava syndrome, characterized by facial erythema and jugular vein distention that progress to cyanosis and facial edema when both arms are kept raised over the head (Pemberton sign)

Diagnosis 

-Serum TSH, thyroid ultrasound, Fine-needle aspiration (FNA)

-radionuclide thyroid scanning

-the diagnostic procedure of choice is FNA 

Treatment 

Medical therapy, levothyroxine suppressive therapy, surgery, RAI therapy, Ultrasound-guided radiofrequency ablation

-thyroid surgery is indicated for patients with Graves disease, toxic multinodular goiter, toxic adenoma, Reidel’s thyroiditis, goiter, thyroid nodules benign and malignant thyroid tumors 

-Complications of thyroid surgery: injury to recurrent laryngeal nerve with resultant vocal cord paralysis, hypoparathyroidism, injury to cervical sympathetic trunk resulting in Horner’s syndrome 

Radioactive iodine-131 is used for treatment of thyrotoxicosis, thyroid cancer and for diagnostic thyroid scanning

-It is effective in ablating the thyroid gland and producing permanent hypothyroidism

-In North America, RAI forms the mainstay of Graves’ disease 

– the only isotope used for treatment of thyrotoxicosis is 131I

-RAI is most often used in older patients or those who have relapsed after medical or surgical therapy or in whom medical or surgical therapy is contraindicated 

-Radioactive iodine should not be given to pregnant women due to the potential teratogenic effects for the fetus’s growth

-all women of childbearing age must have a negative pregnancy test prior to treatment

-After RAI, wait for 6 months before conceiving 

-Absolute contraindications to RAI: pregnancy or planning pregnancy within 6 months of treatment, breastfeeding 

-Relative contraindications to RAI: children, adolescents, those with ophthalmopathy 

-After RAI treatment, most patients become euthyroid within 2 months 

-The most common complication of RAI is hypothyroidism 

-RAI can exacerbate Graves’ ophthalmopathy especially if the patient is a smoker

Introduction 

Grave’s disease is an autoimmune thyroid disorder characterized

by circulating antibodies that stimulate the TSH receptor, resulting in the increase in synthesis and release of thyroid hormones 

-it is the most common cause of hyperthyroidism and thyrotoxicosis 

-It is more common in women than in men with onset usually between 20 and 40 years of age 

-Dietary iodine supplementation can trigger Graves disease

-Thyrotoxicosis: clinical state resulting from inappropriately high thyroid hormone levels

hyperthyroidism: thyrotoxicosis caused by elevated synthesis and secretion of thyroid hormone

Symptoms & Signs

General: fatigue, fever, heat intolerance, weight change, irritability, intolerance    

Thyroid: diffusely enlarged thyroid often with a loud bruit 

Eyes: infiltrative ophthalmopathy (Graves exophthalmos),spasm of the upper eyelid revealing the sclera above the corneoscleral limbus (Dalrymple’s sign) , lid lag with downward gaze (von Graefe sign), a staring appearance (Kocher sign), conjunctival swelling and congestion, keratitis, papilledema, permanent visual loss 

Nervous: Restlessness, nervousness, fine resting tremors 

Cardiac: palpitations, angina,exertional dyspnea, atrial fibrillation, premature atrial contractions, atrial tachycardia, ischemic or valvular heart disease, pulmonary hypertension    

Gastrointestinal: dysphagia, frequent bowel movements, diarrhea  

Musculoskeletal: muscle weakness, cramps, osteoporosis  

Dermatologic: facial flushing, moist warm skin, pruritis, increased sweating, fine hair, onycholysis,bony involvement leads to subperiosteal bone formation and swelling in the metacarpals (thyroid acropachy), infiltrative dermopathy (pretibial myxedema)

Genitourinary: menstrual irregularities  amenorrhea, decreased fertility, and an increased incidence of miscarriages

Diagnosis 

Serum TSH: low or undetectable 

free T4 or T3: elevated 

Thyroid receptor antibodies (TRAbs): elevated 

RAI scan: elevated uptake and a homogeneous pattern 

Technetium scintigraphy: increased or normal thyroid uptake of technetium 

Treatment 

Symptomatic treatment: beta blockers, calcium blockers 

Antithyroid drugs: Methimazole, carbimazole, propylthiouracil 

Radioactive iodine (131I, RAI): the most commonly prescribed treatment in the United States, but is contraindicated in pregnancy or with breastfeeding 

surgery: a total resection of one lobe and a subtotal resection of the other lobe

Introduction 

Euthyroid sick syndrome is a clinical condition characterized by low thyroid hormone levels  in clinically euthyroid patients with nonthyroidal systemic illness

-it can be precipitated by stresses such as chronic liver failure, renal failure, malnutrition, fasting, starvation, anorexia, diabetic ketosis, and sepsis 

-The first testing abnormality to manifest is low T3 level

Symptoms & Signs 

No signs or symptoms of thyroid dysfunction 

Diagnosis 

Patient’s setting: critical illness, chronic illness, ICU admission etc

No clinical manifestations of thyroid dysfunction 

Labs: TSH: Normal or low 

T4 : Normal or low 

T3, total and free : Low 

Reverse T3 (rT3): High or normal 

Treatment: 

-Treat the underlying nonthyroid illness 

-Thyroid hormone replacement is not beneficial

Introduction 

Riedel’s thyroiditis is a chronic inflammatory disease associated with fibrosis or woody enlargement of all or part of the thyroid gland 

-it is now considered a IgG4-related systemic disease 

-Women in midlife are most often affected 

Symptoms & Signs 

-Symptoms of hypothyroidism when enough thyroid tissue is replaced by fibrous tissue; compressive symptoms of the esophagus, trachea such as dysphagia, dyspnea, hoarseness; a hard, ‘woody’ thyroid gland

Diagnosis 

Gross exam: hard, fixed, ‘woody’ thyroid gland 

Labs: normal or low thyroid hormones, normal or elevated TSH, normal or elevated IgG4 levels 

Open thyroid biopsy: a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and obliterative phlebitis

Treatment 

Surgery: decompression through thyroidectomy Hypothyroidism: thyroid hormone replacement

subacute (de Quervain or Granulomatous) viral thyroiditis

Introduction 

Subacute thyroiditis is an acute painful disease of the thyroid probably caused by a virus or postinfectious inflammation 

-Measles, mumps, influenza, adenoviruses are among the commonly blamed viruses 

-It occurs between 30 and 50 years of age; it is three to five times more common in females than in males 

-It is often associated with HLA-B35

Symptoms & Signs 

Fever, anterior neck pain, aggravated by swallowing; pain frequently refers to the ear; a markedly tender thyroid gland upon palpation with one or more nodules; in the acute phase the patient may be euthyroid or hyperthyroid

Diagnosis 

Labs: Early hyperthyroidism is followed by a hypothyroid phase and later euthyroid phase

Biopsy: Lymphocytes and multinucleated giant cells

Treatment 

Aspirin, NSAIDS, glucocorticoids, β-adrenergic blockers; monitor TSH, T4 every two weeks; Complete recovery in most cases 

Introduction 

Hypothyroidism is a clinical syndrome caused by insufficient thyroid hormone production

-it is 10 times more common in females than in males

-Thyroxine (T4) and triiodothyronine (T3) are the thyroid hormones

-Peripherally, thyroxine T4 is converted to the active triiodothyronine T3

-T3 is three to four times more potent than thyroxine T4. 

-Primary hypothyroidism is caused by the intrinsic dysfunction of the thyroid gland. -The most common cause is Hashimoto’s thyroiditis

-other causes: surgical removal, ablation of thyroid gland 

Secondary hypothyroidism is caused by a deficiency of thyroid-stimulating hormone (TSH) from the pituitary gland or deficiency of thyrotropin-releasing hormone from the hypothalamus

Drug induced hypothyroidism: Amiodarone, lithium, α-interferon, interleukin etc can also cause hypothyroidism 

Symptoms & Signs 

Symptoms: headaches, hair loss, fatigue,lethargy, depression, shortness of breath, constipation, weight gain, menstrual irregularities, infertility, muscle cramps, joint pains, paresthesias, cold intolerance, carpal tunnel syndrome, dysphagia, neck discomfort, decreased hearing  

Signs: Puffy face, periorbital puffiness, loss of outer third of eyebrows, pallor, thickening of the tongue, hoarseness, bradycardia, diastolic hypertension, hypoventilation, absent or decreased bowel sounds, edema, delayed relaxation of ankle jerks, peripheral neuropathy, cool, rough, dry skin, yellowing of skin, thin brittle nails, hypothermia, thinning of hair, peripheral edema, delayed relaxation of deep tendon reflexes, cardiac enlargement (myxedema heart), psychosis (myxedema madness), altered mental status (myxedema coma) 

Diagnosis 

-The single best screening test for hypothyroidism is the serum TSH

-Primary hypothyroidism: High TSH (stimulating the failing gland), with low total or free thyroxine T4 and triiodothyronine T3

-Secondary hypothyroidism: Low TSH with low total or free thyroxine T4 and triiodothyronine T3

-Imaging: CT or MRI may show a goiter in the neck, pituitary hyperplasia 

Treatment 

Synthetic levothyroxine is the preferred medication for treating hypothyroidism 

Hashimoto Thyroiditis

Introduction

-Hashimoto thyroiditis is a common chronic autoimmune inflammatory disease 

-It is the most common  thyroid disorder in the United States

-it is the most common cause of hypothyroidism 

-it is caused by an autoimmune attack on the thyroid

-it is associated with a host of other autoimmune diseases 

-Autoantibodies in Hashimoto thyroiditis are  thyroglobulin antibody (Tg Ab), thyroidal peroxidase antibody (TPO Ab) and the TSH receptor–blocking antibody (TSH-R [block] Ab). 

-It shows female preponderance and is predominantly a disease of middle age 

-It is characterized by destruction of thyroid follicles and infiltration by lymphocytes and plasma cells interspersed by enlarged follicular epithelial oncocytic cells with abundant pink eosinophilic granular cytoplasm (Hürthle cells or Askanazy cells) 

-it is associated with an increased incidence of papillary carcinoma of the thyroid and primary thyroid lymphoma 

Symptoms & Signs 

-Diffusely enlarged, firm, rubbery, nontender and nodular thyroid which becomes smaller with the progression of the disease

-Some patients may develop hypothyroidism or rarely hyperthyroidism and exhibit their clinical manifestations 

Diagnosis 

Thyroid antibodies: Elevated antithyroglobulin and antithyroid peroxidase antibodies 

Laboratory findings vary based on thyroid status 

If patient is euthyroid: normal TSH and normal thyroid hormones 

if hypothyroid, elevated TSH and low thyroid hormones 

if hyperthyroid, suppressed TSH and elevated thyroid hormones 

FNAB: thyroid gland infiltrated by lymphocytes and Hürthle cells or Askanazy cells

Treatment 

Symptomatic/Cosmetic reasons: Surgery 

Hypothyroid status: Thyroid replacement therapy

Introduction

Hyperprolactinemia is a condition of elevated prolactin level in blood 

-Prolactin is a pituitary hormone which acts to induce and maintain lactation and to decrease reproductive function and libido via via suppression of gonadotropin-releasing hormone [GnRH]

-Dopamine suppresses the production of prolactin from the anterior pituitary, so dopamine antagonists are associated with hyperprolactinemia

-The most common cause of hyperprolactinemia is a prolactin-secreting pituitary adenoma. Other causes are hypothyroidism, hypothalamic masses, 

and medications (risperidone, haloperidol, chlorpromazine, perphenazine, SSRIs, metoclopramide, opiates, H2 antagonists)

Symptoms & Signs

Men: Erectile dysfunction, loss of libido, gynecomastia, headaches, visual symptoms 

Women: loss of libido, amenorrhea, oligomenorrhea, infertility, irritability, anxiety, depression, galactorrhea and osteoporosis  

Diagnosis 

Labs: Fasting prolactin levels; labs to rule out other conditions such as hypothyroidism, pregnancy 

Imaging: Pituitary MRI

Treatment 

Dopamine agonists: Primary treatment of hyperprolactinemia; cabergoline, bromocriptine, or quinagolide

-Cabergoline is the preferred drug for the treatment of hyperprolactinemia because of greater efficacy and lower adverse effects

-Cabergoline can cause valvular heart disease 

Levothyroxine: if hypothyroidism is the cause of hyperprolactinemia 

Surgery: Transsphenoidal pituitary surgery for adenomas which are resistant to medical therapy 

Introduction 

Acromegaly and gigantism are hormonal disorders caused by excessive growth hormone secretion usually due to a pituitary tumor 

-Acromegaly develops if excessive GH exposure occurs after closure of the long bone epiphyses (Adults = Acromegaly); where as gigantism develops if it occurs before closure of the epiphyses 

-Grown hormone hypersecretion leads to excessive generation of IGF-1, which acts as the mediator of most of the effects of GH 

-The average age at the time of diagnosis is 40 to 45 years 

Symptoms & Signs 

Facial Features: Frontal bossing, macroglossia, Jaw enlargement  (prognathism), widened teeth spacing 

Musculoskeletal features: Increased hat, shoe, glove and ring size; Enlargement of hands and feet with a doughy texture; arthropathy, carpal tunnel syndrome, kyphoscoliosis 

ENT: Large fleshy nose, deepening of the voice, snoring 

Skin: Doughy texture, cutis verticis gyrata, acanthosis nigricans, skin tags, thick heel pads, hyperhidrosis, hirsutism 

Eyes: Bitemporal hemianopsia (due to optic chiasm compression from the tumor) 

Associated conditions: Diabetes, hypertension, glucose intolerance, cardiomyopathy, left ventricular hypertrophy, diastolic dysfunction

Diagnosis 

Insulin-like growth factor – 1 : Elevated levels 

Growth hormone: Elevated levels in serial measurements; Failure to suppress Growth hormone levels by oral glucose-tolerance test 

Imaging: MRI of the pituitary may show macroadenoma 

Treatment 

Surgery: Removal of adenoma by transsphenoidal surgery 

Somatostatin analogues: Octreotide, lanreotide, pasireotide

Dopamine agonists: Bromocriptine, cabergoline 

GH receptor antagonist: Pegvisomant  

Radiation: Pituitary irradiation 

Q. What is the most important requirement for diagnosis of GH excess? Demonstration of unsuppressable GH secretion 

Introduction 

Chromoblastomycosis is a chronic progressive subcutaneous mycosis caused by multiple species of pigmented fungi, known as melanized or ‘dematiaceous’ fungi, mainly the Fonsecaea, Phialophora, or Cladosporium species

-the fungi appear as brown, thick-walled, spherical, septal cells in tissues (Medlar bodies or muriform cells) 

-it usually affects older male agricultural workers 

-it typically occurs on the foot or leg, arms or trunk following tissue injury due to trauma  

-it occurs in the Americas, Africa (particularly Madagascar), and South Asia 

Symptoms & Signs 

-the fungus forms thick-walled single cells or cell clusters (sclerotic or muriform bodies), which may transform into papules, scaly, wart-like structures resembling the tips of a cauliflower, and verrucous plaques with satellite lesions 

Diagnosis 

Histology: brown-pigmented, thick double-walled, multiseptate, melanized sclerotic, globose structures called muriform bodies. 

Culture: fungi grow as darkly pigmented black colonies with a downy surface 

Treatment 

Antifungals: Itraconazole,voriconazole, terbinafine, flucytosine, amphotericin Procedures: Cryotherapy, curettage, electrodessication, and surgical excision

Introduction 

Penicilliosis is a tuberculosis-like fungal disease caused by Talaromyces (formerly Penicillium) marneffei

–It is most common in northeastern India, Thailand, Vietnam,Taiwan, China, and Hong Kong

-it most often affects patients with advanced HIV

-it is a dimorphic fungus; grows as a mold that produces a distinctive rose-colored pigment and as yeast-like cells that reproduce with septal formation 

-it is acquired by spore inhalation

Symptoms & Signs 

-It usually presents as a pulmonary disease or disseminated disease 

-Fever, fatigue, cough, weight loss, lymphadenopathy, hepatosplenomegaly, generalized umbilicated papular rash resembling molluscum contagiosum 

Diagnosis 

The diagnosis is made by culture or by histology 

-it forms characteristic yeast-like cells which are divided by a septum and produce a characteristic red pigment

Treatment 

The treatment of choice consists of amphotericin B followed by itraconazole 

Introduction 

Sporotrichosis is a chronic granulomatous fungal infection caused by Sporothrix schenckii

-it is common among gardeners, florists and agriculture workers 

-Infection occurs when the organism is inoculated into the skin during gardening or puncture from a rose thorn 

S. schenckii is a thermally dimorphic fungus which produces branching, septate hyphae and conidia 

Symptoms & Signs 

Sporotrichosis has four clinical presentations: 

Fixed: a painless nodule or plaque that may become pustular or ulcerated or verrucous plaque; most common on dorsum of hand or finger

Lymphocutaneous:  Erythematous nodules in a linear array in lymphatic channels mostly on the dorsum of the hand and forearm

Pulmonary: inhalation of conidiospores producing pulmonary infection 

Disseminated:  From lungs,it disseminates hematogenously to joints, eyes and meninges 

Diagnosis 

Histology: Granulomatous microabscesses 

Culture: Most reliable method of diagnosis 

Treatment 

Itraconazole, fluconazole, terbinafine, Amphotericin B, potassium iodide 

Introduction

-Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis

-It occurs in rural areas of South and Central America, thus known as South American blastomycosis

-It is a dimorphic fungus that exists as a mold in soil and as a yeast in tissue

-The mold produces chlamydospores and conidia which enter human body mainly by inhalation 

Symptoms & Signs 

Asymptomatic form: marked by long asymptomatic periods 

Pulmonary form: Cough, weight loss, pulmonary granulomas 

Mucocutaneous form: Oropharyngeal lesions are the most common sign on physical examination; they present as small granulomas or painful ulcers over the nose, conjunctivae, mouth, gingiva, lips, pharynx, larynx (dysphonia) or anus 

Lymphatic form: Lymphadenopathy, ulceration, draining sinuses 

Diagnosis 

Histology: Granulomas with central caseation with fibrosis 

Culture: A parent round yeast cell surrounded by large numbers of small buds described as ‘Ship captain’s wheel’ 

Serology: antigen detection, antibodies to paracoccidioidin 

Treatment 

Effective agents: Itraconazole (the drug of choice), Voriconazole, ketoconazole, trimethoprim-sulfamethoxazole and Amphotericin B