Week 21

Clinical approach

100

A patient presents with weakness of downward movement when looking medially where is the lesion? 

Right Trochlear nerve 

200

What is the screening test and stimulation test for assessment of CRH/ACTH? 

Screening test: early morning cortisol 

Stimulation test: Short synacthen test 

300

What features would you expect to see in hypertensive retinopathy? 

Based on grade, changes

include:

Silver wiring

Arterio-Venous nipping

Cotton wool spots

Flame haemorrhages

Papilloedema

400

What are the clinical features of reduced GH? 

Reduced exercise capacity,reduced lean muscle mass,

impaired psychological well being

Metabolic consequences - hyperinsulinaemia,reduced glucose

tolerance,raised total, LDL cholesterol and triglycerides.

500

List some causes for Hypopituitarism 

• Mass lesions (pituitary or hypothalamus)

- Pituitary tumours – non-functioning

- Metastases, craniophyaryngiomas, meningiomas

- Infiltrative disease – sarcoidosis, haemochromatosis, lymphocytic hypophysitis, granulomatous

hypophysitis

- Infection – abscess,TB

-  Head injury

• Iatrogenic

- Irradiation or Post operative

- Checkpoint inhibitor immunotherapy toxicity - eg melanoma

- Hypophysitis and primary hypothyroidism most common endocrinopathies

• Infarction

- Apoplexy

- Sheehan’s syndrome – infarction of enlarged postpartum gland usually associated with post partum heamorrhage

• ‘Empty sella syndrome’

-  normal anatomical variant, pit dysfunction approx 10%

• Isolated hormone abnormalities

- Idiopathic Hypogonadotrophic hypogonadism, (Kallmann Syndrome with anosmia) - several genesassociated

Tumours/ neoplasia

100

What are chromophobes, and how do they appear histologically?

Chromophobes:

• Pale/white-staining cells
• Stem cells or degranulated/poorly granulated cells
• Do not stain strongly with routine histological dyes

200

in MEN 2B where would you expect to find neoplasms? 

- Medullary thyroid

- Adrenal medulla 

- Mucosal neuroma 

- Marfanoid body habitus 

300

Name the two main categories of chromophil cells and identify the hormone-producing cell types found within each category?

 

Acidophils:

• Somatotrophs (growth hormone-producing cells)
• Lactotrophs (prolactin-producing cells)

Basophils:

• Thyrotrophs (TSH-producing cells)
• Corticotrophs (ACTH-producing cells)
• Gonadotrophs (FSH and LH-producing cells)

400

What are the histological features of Hurthle cells and what pathology are they associated with? 

Some follicular adenomas 

• Brightly eosinophilic  abundant cytoplasm = packed with   nonfunctional mitochondria

500

List the major differential diagnoses for a diffuse, non-nodular goitre:

Causes of a non-nodular (diffuse) goitre include:

• Pregnancy
• Simple colloid goitre
• Graves disease
• Hashimoto's thyroiditis (diffuse phase)
• Drug/chemical-induced goitre
• Dietary goitre (e.g., iodine deficiency or goitrogen exposure)
• Low-grade B-cell lymphoma
• Dyshormonogenetic goitre

Hormones

100

What is the biochemical definition of subclinical hyperthyroidism  

Low TSH with normal FT4

200

What anterior pituitary hormone/s does somatostain inhibit? 

GH and TSH

300

What are the two hypothalamic output mechanisms? 

1. Neuroendocrine

Anterior pituitary (target) hormones:

Stimulatory : GHRH, GnRH, CRH,TRH

Inhibitory : Dopamine (DA) and Somatostatin (SS)

2. Neural pathways

Posterior pituitary: Neurosecretory granules synthesised in hypothalamus

travel down neurons are released into circulation in post pituitary

400

Name the anterior pituitary cells types that secrete each hypothalamic hormone.  

Somatotroph= GH

Lactotroph= Prolactin

Thyrotroph = TSH

Corticotroph= ACTH

Gonadotroph =FSH, LH

500

Describe the sequence of events by which TSH stimulates the synthesis, storage, and release of thyroid hormones (T3 and T4) from thyroid follicular cells

• TSH binds to its membrane receptor on thyroid follicular cells. 
• This stimulates iodide uptake from the blood via increased expression of the Na⁺/I⁻ symporter (NIS); iodide is then transported into the colloid. 
• TSH stimulates thyroglobulin (Tg) synthesis, a large glycoprotein that forms the major component of the colloid. 
• TSH increases thyroid peroxidase (TPO) activity, which oxidises iodide and incorporates it into tyrosine residues on thyroglobulin (organification).
• Iodinated tyrosine residues undergo coupling reactions to form T3 and T4, which remain stored within thyroglobulin in the colloid. 
• When thyroid hormone is required, iodinated thyroglobulin is endocytosed back into the follicular cell and degraded within lysosomes, releasing T3 and T4.
• T3 and T4 are secreted into the bloodstream via the MCT8 transporter, a process also regulated by TSH.

Endocrine pathology

100

What visual field defect is expected in a pituitary adenoma? Explain why? 

Bitemporal Hemianopia, compression of the optic chiasm resulting in loss of input from the nasal retinal nerves. 

200

Define autoimmunity and autoimmune disease, and state one key difference between them

• Autoimmunity is the production of autoantibodies or activation of T cells that react against self-antigens.
• Autoimmune disease is self-reactivity that results in tissue pathology and clinical disease.
• The key difference is that autoimmunity may exist without tissue damage, whereas autoimmune disease causes pathology. 

300

Compare systemic autoimmune diseases with organ-specific autoimmune diseases. Include the predominant hypersensitivity mechanism and one example of each

• Systemic autoimmune diseases affect multiple organs and tissues.
• They are predominantly mediated by Type III hypersensitivity reactions (immune complexes).
• Organ-specific autoimmune diseases primarily affect one organ or tissue. 
• They are predominantly mediated by Type II and/or Type IV hypersensitivity reactions. Example: Graves disease or Hashimoto thyroiditis. 

400

Explain the immunopathology of Hashimoto thyroiditis and Graves disease, highlighting two key differences.

• Hashimoto thyroiditis is primarily a destructive autoimmune disease causing thyroid follicle destruction by autoreactive T and B cells.
• Graves disease is caused by stimulating TSH receptor antibodies (TRAbs) leading to hyperthyroidism.
• Hashimoto disease is associated with anti-TPO and anti-thyroglobulin antibodies. 
• Graves disease shows follicular hyperplasia and scalloped colloid. 
• Hashimoto causes hypothyroidism whereas Graves disease causes hyperthyroidism. 

500

Describe the role of central and peripheral T-cell tolerance in preventing autoimmune disease.

• Central tolerance occurs in the thymus where autoreactive T cells are eliminated by apoptosis (negative selection). 
• Medullary thymic epithelial cells express tissue-restricted antigens under the control of AIRE and FEZF2. 
• Peripheral tolerance controls self-reactive T cells that escape central tolerance.
• Mechanisms include ignorance, anergy, quiescence, exhaustion, and suppression by regulatory T cells. 
• Failure of central or peripheral tolerance can result in autoimmune disease due to loss of self-tolerance. 

Lucky dip

100

What blood test can be used to test for LV stretching? 

B-type natriuretic peptide- release by cardiac muscle mostly LV, normal level excludes HF 

200

How can ACE inhibitors and ARBs cause hyperkalemia?

Increase Na+ and H2O excretion from the urine --> meaning that K+ is not excreted in the urine = more remains in body = hyperkalemia

300

Outline the 2 main categories of asthma

1. Eosinophilic / Allergic >80%

• More associated with atopy = genetic predisposition to IgE mediated inflammation causing asthma, allergic

  rhinitis and/or eczema. Family history very common

• Steroid responsive

2. Neutrophilic / Non-Allergic <20%

• Not associated with atopy 
• Less steroid responsive 
• Typically mature age onset
• Associated with GORD 
• (COPD associated inflammation is also neutrophilic)

400

DSM 5 criteria for Manic episode: 

≥3 of the following: ("DIGFAST") - lasting at least 1 week

• Distractibility 
• Impulsitivity 
• Grandiosity or ↑ self-esteem 
• Flight of ideas (racing thoughts)
• Activity increase (with high potential for painful consequences)
• Sleep deficit (less need for)
• Talkativeness or pressure to keep talking 

500

Outline the difference between a Gohn focus and Ranke complex

• Gohn focus = initial site of infection in the lung where MTb establishes itself & beings to form a granuloma
• Localised inflammation
• Necrotic core 
• Usually develops peripherally, sub-pleural & in region of interlobar fissure, with associated hilar lymph node drainage 
• Ranke complex = dystrophic calcification and fibrosis of the Gohn complex