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Effects of Hypothyroidism on Serum Lipids


HYPOTHYROIDISM AND LIPIDS
small increase in LDL-C, total chol, and a decr in HDL-C
hypothyroid liver produces less bile
less mobilization of TGs, less lipoprotein lipase activity
decreased uptake of lactate
diminished oxidation of other (non-lipid) substrates
lipogenesis decreased in hypothyroid livers
cholesterol synthesis stays the same
composition and the transport of lipoproteins seriously disturbed
hypothyroidism characterized by hypercholesterolaemia
marked increase in low-density lipoproteins (LDL) and apolipoprotein B (apo A) decreased fractional clearance of LDL
reduced number of LDL receptors in the liver
high-density lipoprotein (HDL) levels are normal or even elevated
dt decr activity of cholesteryl-ester transfer protein (CETP) & hepatic lipase (HL)
low activity of CETP and HL-->reduced transport of cholesteryl esters from HDL2 to very low-density lipoproteins (VLDL) and intermediate low-density lipoprotein (IDL), and reduced transport of HDL2 to HDL3
hypothyroidism incr oxidation of plasma cholesterol
dt altered pattern of binding and to the increased levels of cholesterol
cardiac oxygen consumption is reduced
this assoc w/ incr peripheral resistance and reduced contractility
often accompanied by diastolic hypertension + dyslipidemia-->atherosclerosis
changes in lipoproteins correlate with changes in free thyroxine (FT4) levels

subclinical hypothyroidism
associated with normal or slightly elevated total cholesterol levels
increased LDL, and lower HDL
associated with endothelium dysfunction, aortic atherosclerosis
& myocardial infarction
lipid disorders exhibit great individual variability

GUYS WITH LOW THYROID
not cold dt testosterone
sx: depression, lost edge, weight gain, lipids off
much more prevalent now than before
far more prevalent in women but men not dxd dt not having classic signs

MCALLISTER ON HYPOTHYROID EFFECT ON LIPIDS:
enzyme that converts chol to prenenolone is thyroid dependent
so low thyroid-->less prenenolone-->high chol and low sex hormones
looks to me like the enzyme is in all mitochondria
and thyroid affect not mentioned here

from wikipedia:
Pregnenolone is synthesized from cholesterol. This conversion involves hydroxylation at the side-chain at C20 and C22 positions, with cleavage of the side-chain. The enzyme performing this task is cytochrome P450scc, located in the mitochondria, and controlled by pituitary tropic hormones, such as ACTH, FSH, LH.

Cytochrome P450, family 11, subfamily A, polypeptide 1 (P45011a1), often referred to as P450scc (or 20,22-desmolase), is a mitochondrial enzyme associated with the conversion of cholesterol to pregnenolone. The gene name is CYP11A1.[1] The term "desmolase" is becoming outdated and the enzyme is now commonly referred to as P450scc, where "scc" refers to side-chain cleavage.

The protein is a member of the cytochrome family of enzymes. It catalyzes the first step in all steroid hormone production -- the conversion of cholesterol to pregnenolone, the first steroid formed:

cholesterol + reduced adrenal ferredoxin + O2 \rightleftharpoons pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin + H2O

The protein resides on the inner mitochondrial membrane, facing the interior (matrix).[2] The presence of this enzyme defines if a cell is steroidogenic. Consequently, P450scc is found in all steroid-producing cell types such as theca cells and luteal cells in the ovary, Leydig cells in the testis, and cell types in the adrenal cortex.

TOTAL TESTOSTERONE
low 500-700-900-1000 high
under 400 too low
about 40% of pop meets criteria for hypogonadism (HIM study)
HIM: hypogonadism in males

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