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BI11.1-2 | Organ Function tests and Hormones — Part 2

Proteinuria and Urinalysis in Renal Disease

Urinalysis is a critical complement to the serum RFT panel.

Figure: Proteinuria and Urinalysis in Renal Disease

Proteinuria (protein in urine) indicates glomerular damage:
- Normal: <150 mg/day
- Nephrotic syndrome (>3.5 g/day): massive proteinuria causing hypoalbuminaemia → oedema, hyperlipidaemia, lipiduria. Common causes in India: minimal change disease (children), membranous nephropathy, diabetic nephropathy (major cause — DM is epidemic in South India)
- Nephritic syndrome (<3.5 g/day + haematuria + hypertension + oliguria): seen in post-streptococcal GN (still common in India), IgA nephropathy

Urine specific gravity and osmolality: reflect tubular concentrating ability. In established CKD, specific gravity becomes fixed at ~1.010 (isosthenuria) — tubules can no longer concentrate or dilute.

Microalbuminuria (30–300 mg/day albumin): earliest detectable marker of diabetic nephropathy, preceding overt proteinuria by years. Routine annual screening in all diabetics is WHO/ADA-recommended — this is now part of NMC competency expectations.

Thyroid Function Tests — The HPT Axis

Thyroid Function Tests (TFT) assess the hypothalamic-pituitary-thyroid (HPT) axis.

Figure: Thyroid Function Tests — The HPT Axis

The TFT panel:

Test	Normal Range	Interpretation
TSH (Thyroid-Stimulating Hormone)	0.4–4.0 mU/L	Best screening test — first-line
Free T4 (fT4)	9–25 pmol/L	Active thyroxine available to tissues
Free T3 (fT3)	2.6–5.7 pmol/L	Active T3 (more potent) — measured when T3 toxicosis suspected
Total T4/T3	Varies	Affected by binding proteins — less useful
Anti-TPO antibody	<35 IU/mL	Elevated in Hashimoto's, Graves' (autoimmune)
Anti-TSH receptor Ab	Negative	Elevated in Graves' disease

The feedback loop: Hypothalamus → TRH → Pituitary → TSH → Thyroid → T4/T3 → negative feedback to both hypothalamus and pituitary.

Interpreting TFT patterns:

TSH	fT4	Diagnosis
↑ High	↓ Low	Primary hypothyroidism (thyroid failure)
↓ Low	↑ High	Primary hyperthyroidism (Graves', toxic nodule)
↓ Low	↓ Low	Secondary hypothyroidism (pituitary/hypothalamic failure)
↑ High	↑ High	TSH-secreting pituitary adenoma (very rare)
↑ High	Normal	Subclinical hypothyroidism

TSH is the best single screening test — pituitary TSH responds sensitively to even minor changes in thyroid hormone levels. A normal TSH virtually excludes primary thyroid disease. However, TSH alone is insufficient when pituitary disease is suspected — always check fT4 too.

Figure: Interpreting TFT patterns:

Thyroid Disorders in India — Clinical Context

Hypothyroidism is extremely prevalent in India — estimated 42 million people affected. It is the commonest endocrine disorder in women.

Figure: Thyroid Disorders in India — Clinical Context

Hashimoto's thyroiditis (autoimmune hypothyroidism): the commonest cause. Anti-TPO antibodies attack the thyroid gland → progressive destruction → goitre initially → atrophy later. TFT: high TSH, low fT4, positive anti-TPO.

Iodine deficiency remains a cause in certain Himalayan and inland regions despite the National Iodisation Programme. It causes goitre and, in pregnancy, cretinism (congenital hypothyroidism → intellectual disability, growth retardation). India has a National Iodine Deficiency Disorders Control Programme.

Hyperthyroidism — Graves' disease: autoimmune; TSH-receptor stimulating antibodies mimic TSH → uncontrolled thyroid hormone production. Features: tremor, palpitations, heat intolerance, exophthalmos (proptosis), pretibial myxoedema. TFT: low TSH, high fT4/fT3, positive anti-TSH receptor Ab.

Thyroid hormones and biochemistry cross-link: T4 and T3 are iodinated thyronines synthesised from tyrosine residues on thyroglobulin. They require iodine, which is actively transported into thyroid follicular cells via the sodium-iodide symporter (NIS) — inhibited by thiocyanates in cassava and certain cruciferous vegetables (of relevance in cassava-belt regions of Kerala/Tamil Nadu).