Non-medicalization of medical science: Rationalization for future

Table 5 Clinical spectrum of preclinical conditions: Looking at hard facts

	Prediabetes	Subclinical hypothyroidism	Osteopenia	MACS
Clinical disease	Diabetes	Overt primary hypothyroidism	Osteoporosis	Cushing’s syndrome
Prevalence of preclinical condition	5.5%-53.1%[43], IFG -6.2%[41], IGT -10.6%[41]	4.3%-15%[20]	54%-80%[65]	5%-48%[6]
Prevalence of clinical condition	10.5%[41]	0.2%-5.3%[19]	2%-26.3%[64]	0.3% of patients with adrenal incidentalomas[5]
Dx criteria	FPG: 100-125, 2-h PPG: 140-199, HbA1C: 5.7-6.4	Elevated TSH level with a fT4 level that is within the population specific range	T-score between -1 to -2.5	Abnormal 1-mg dexamethasone suppression test with absent stigmata of Cushing’s disease.
Progression	5%-18.3%[54,55,60]	2%-6%[22]	16% risk of major osteoporotic fracture in 10 years[67]	< 1%[13]
Regression/reversal	19%[54]	60%[21]	Stays static or progresses	2%-44%[6,11]
Long-term sequelae	Microvascular and macrovascular complications of diabetes, Cardiovascular risk	Markers of cardiovascular function (such as left ventricular diastolic function) and lipid profile deteriorate with subclinical hypothyroidism	Fractures	Hypertension, Diabetes, Dyslipidemia, Osteoporosis
Short-term consequences		Fatigue, muscle weakness, cold intolerance
Preventive options	Lifestyle and behavioural therapy, drugs	Lifestyle and behavioural therapy, drugs	Lifestyle and behavioural therapy, drugs	Lifestyle and behavioural therapy, drugs, surgery
Pharmacotherapy	Metformin	L-thyroxine	Calcium and vitamin D	Mifepristone, metyrapone
Surgery	-	-	-	Adrenalectomy
True prevention	x	x	x	x
Adverse effects of treatments available	B12 deficiency	Bone loss, cardiac arrhythmias in elderly	Overtreatment can predispose to hypervitaminosis D	Hypocortisolism
Recommendations/Guidelines	Metformin should be considered in those with BMI ≥ 35 kg/m2, those aged < 60 yr, and women with prior gestational diabetes mellitus with IGT	TSH > 10 mIU/L, consider treatment; TSH < 10 mIU/L, consider treatment if symptoms suggestive of hypothyroidism, positive antibodies to thyroid peroxidase, or evidence of atherosclerotic cardiovascular disease, heart failure, or risk factors for these diseases	Country-specific guidelines for treatment	Individualized approach to consider patients with ‘autonomous cortisol secretion’ due to a benign adrenal adenoma and comorbidities potentially related to cortisol excess for adrenal surgery
Grade of recommendation	Level of evidence A[58]	Grade B, BEL 1 (Best evidence rating level)[36]	-	(⊕OOO) Very low level of evidence/recommendation[3]

MACS: Minimal autonomous cortisol excess; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; FPG: Fasting plasma glucose; HbA1C: Hemoglobin A1c; PPG: Photoplethysmography; TSH: Thyrotropin; BMI: Body mass index.