Riedel’s thyroiditis


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


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


Surgery: decompression through thyroidectomy Hypothyroidism: thyroid hormone replacement

Subacute de quervain thyroiditis

subacute (de Quervain or Granulomatous) viral thyroiditis


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


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

Biopsy: Lymphocytes and multinucleated giant cells


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



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) 


-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 


Synthetic levothyroxine is the preferred medication for treating hypothyroidism 

Hashimoto thyroiditis

Hashimoto Thyroiditis


-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 


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


Symptomatic/Cosmetic reasons: Surgery 

Hypothyroid status: Thyroid replacement therapy



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  


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

Imaging: Pituitary MRI


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 

Acromegaly & Gigantism


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


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 


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 



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 


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 


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

Talaromyces or Penicilliosis


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 


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


The treatment of choice consists of amphotericin B followed by itraconazole 



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 


Histology: Granulomatous microabscesses 

Culture: Most reliable method of diagnosis 


Itraconazole, fluconazole, terbinafine, Amphotericin B, potassium iodide 



-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 


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 


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




Blastomycosis is a fungal infection caused by inhaling Blastomyces dermatitidis

-B. dermatitidis is a dimorphic fungus that exists as a mold in soil and as a yeast in tissue

-In the United States, it is endemic in the states bordering the Great Lakes and in the Mississippi River basin

-Its geographic location is similar to that of histoplasmosis 

-in soil it forms hyphae with small pear-shaped conidia

-Infections occur from inhalation of aerosolized conidia, which transform to the yeast phase in the lungs 

Symptoms & Signs 

-The most common sites of involvement in blastomycosis are lung, skin, bone, genitourinary tract, and central nervous system

Lungs: chief sites of involvement; may cause lobar pneumonia indistinguishable from bacterial pneumonia; fever, chills, cough, chest pain, and dyspnea 

Skin: the most common extrapulmonary form of blastomycosis; either verrucous or ulcerated in appearance

Bone: osteomyelitis frequently affecting the ribs and vertebrae 

Genitourinary tract:  causes epididymitis, prostatitis, and urethritis

CNS: causes meningitis, mass lesions, or brain abscess


Histology:  Rounded, double walled, spherical cells with broad-based buds (Cryptococcus neoformans forms a narrow-based bud)

Culture: most reliable; Hyaline branching septate hyphae with small pear-shaped conidia

Serology: detects Blastomyces antigen in urine and serum 

Imaging: Lobar consolidation on CXR or CT Chest


Itraconazole (the drug of choice), Voriconazole, Posaconazole, and Amphotericin B 



Aspergillosis is a spectrum of diseases caused by Aspergillus species, most commonly by Aspergillus fumigatus 

-it is the most common invasive fungal infection in transplant recipients and in patients with hematologic cancer 

-it produces small conidia which are inhaled; following inhalation conidia germinate to produce hyphae that invade the lungs and other tissues 

Symptoms & Signs 

 The lungs, sinuses, brain and skin are the organs most often involved.

Allergic bronchopulmonary aspergillosis (ABPA): 

-ABPA is a hypersensitivity reaction to the presence of Aspergillus in the bronchi

-Dyspnea, wheezing, cough, malaise, fever, hemoptysis, bronchiectasis

-Characteristic radiographic finds: “Tramline shadows” (parallel linear shadows); “finger in glove” opacity (due to mucoid impaction in dilated bronchi); “toothpaste shadows” (due to mucoid impaction of the bronchi); “ring shadows” (due to dilated bronchi) 

-The screening test for ABPA is a skin prick test with Aspergillus antigens

Severe Asthma with Fungal Sensitivity 


-The most common syndrome associated with aspergillosis is pneumonia

-Fever, chest pain, cough, hemoptysis 

-Aspergilli have remarkable ability to grow in lung cavities created by tuberculosis; within the cavities, they produce radiopaque aspergillomas (fungus balls) 


-Aspergillus is the most common cause of fungal sinusitis

-Fever, headache, sinus discharge, epistaxis, tissue destruction, necrotic lesions in the nose or palate


-Disseminated aspergillosis can spread to the brain

-headache, fever, neck rigidity, mental status changes 


-Erythematous plaques progressing to necrotic ulcers with black eschars 


Biopsy: Septate, branching hyphae with radiating chains of conidia in V or Y shaped branches 

Serology: Detection of Aspergillus antigens, Galactomannan and 1,3-β-D-glucan


Antifungal drugs: Voriconazole, posaconazole, itraconazole, isavuconazole, micafungin, caspofungin, and amphotericin B 

ABPA: Systemic corticosteroids, antifungals 



Cryptococcosis is a subacute or chronic infection caused by Cryptococcus neoformans, an encapsulated budding yeast

-Cryptococcal cells are typically present in bird droppings, particularly pigeon droppings 

C. neoformans is a yeast that is characterized by a thick polysaccharide capsule. 

-Polysaccharide capsule is the major virulence factor and basis for antigen testing

-it is most common cause of fungal meningitis

-Cryptococcosis is acquired by inhaling aerosols containing the yeast, which disseminate to other organs via blood 

Symptoms & Signs 

-The most common sites of infection are the lungs, central nervous system and skin 

Pulmonary cryptococcosis 

it is often asymptomatic or may cause an influenza-like illness with cough, fever, chest pain and dyspnea 


-Meningitis is the most commonly recognized and most serious form of cryptococcal disease

-In immunocompetent patients, it takes a slow, indolent course but in immunocompromised patients, it takes a more rapid course 

-Headache, fever, nausea, vomiting, neck stiffness, dizziness, somnolence, irritability, confusion, photophobia, seizures, cranial nerve defects, confusion, mental status changes

Cryptococcal skin disease: 

Cryptococcal cellulitis: resembles bacterial cellulitis, red, hot, tender plaques 

Cryptococcal dermatitis: resembles molluscum contagiosum, papular, nodular lesions with central umbilication 

Immune Reconstitution Syndrome

-A paradoxical clinical worsening which comes with enhanced inflammatory response due to immune reconstitution 

-worsening meningitis, increased intracranial pressure, hypercalcemia 


Histopathology and Cytology: globose or oval to lemon-shaped yeast with a polysaccharide capsule after staining with India ink, Gomori methenamine silver (GMS) and periodic acid–Schiff (PAS) stain, Mayer’s mucicarmine stain, and Masson–Fontana melanin stain; On diphenolic substrate, the phenol oxidase of cryptococcus produces melanin in the cell walls producing brownish colored colonies 

Antigen detection:  detection of Cryptococcal capsular antigen in serum, CSF, pleural fluid  

Culture: whitish mucoid colonies with spherical budding yeast cells surrounded by a thick non-staining capsule 

CSF: increased opening pressure, increased protein, decreased glucose, presence of cryptococcal capsular antigen

Imaging: Cryptococcal granulomatous calcifications on CXR; cryptococcomas in the brain on MRI, CT scan 


Pneumonia: Fluconazole, itraconazole, voriconazole, posaconazole

Meningitis: Amphotericin B, Fluconazole