Severe insulin resistance, diabetes mellitus, hypertriglyceridemia, and pseudoacromegaly.

Abstract

A 24-yr-old female student born of apparently normal, unrelated parents presented with severe abdominal pain and muscle cramps at the age of 20 yr. She had also noticed increasing hirsutism and well-developed muscles in her limbs despite making no special effort to exercise beyond her normal activities. These symptoms dated from about the age of 11 yr when she had attained menarche. Her menstrual periods were regular. On physical examination she was tall (179.5 cm) and weighed 74.9 kg with a BMl of 24.0 kg / m2. Her supine blood pressure was 130180 mmHg. She was muscular with welldeveloped leg muscles (Fig. l), large hands ( Fig. 2) and feet, wide shoulders, and a prominent mandible with widely separate teeth giving her an appearance reminiscent of acromegaly. She had a normal amount of subcutaneous fat on her face, abdomen, and chest, but had excessive fat around her neck (Fig. 3) with very little subcutaneous fat on the arms and legs. Acanthosis nigricans was noted in both axillae and groins (Fig. 4). She also had moderate facial hirsutism and a male escutcheon, but no clitoromegaly or temporal hairline recession.An ultrasound scan of her abdomen showed the left ovary to be 4.5 X 3.9 X 3.1 cm and the right ovary to be 7.4 X 4.9 X 5 cm. In both abnormal multiple small cysts were present.The results of selected laboratory investigations are shown on Table 1. She had marked hypertriglyceridemia.Furthermore, her sex-hormone-binding globulin levels were low and therefore, despite normal total testosterone levels, her free androgen index was high. The serum electrolyte (Na+, K+, Ca2+, and Mg'+) concentrations were normal.Glucose tolerance, insulin sensitivity, and p-cell function, A 75-g oral glucose tolerance test (OGTT) revealed diabetes mellitus. Her GH levels were undetectable throughout the

Glucocorticoids and insulin resistance: old hormones, new targets

“…Similarly, the association between low birthweight and subsequent insulin resistance could be explained if the insulin resistance includes insulin-mediated growth and development in utero. However, in support of the original hypothesis, there are rare examples of mutations resulting in dissociation of the growth-promoting and glucoseregulating actions of insulin [101]. Moreover, although homozygous mutations of the insulin receptor cause a clinical syndrome including lipoatrophy [7], transgenic animals with global insulin resistance due to heterozygous multiple mutations of the insulin receptor signalling pathway do turn out to be obese with other features of the metabolic syndrome [102].…”

Insulin-mediated "pseudoacromegaly"

“…[8][9][10] The first case of insulin-mediated pseudoacromegaly was reported in 1993 by Flier et al 11 Since the original case report, at least 7 more patients with similar clinical and biochemical features have been reported in the literature. 3,[12][13][14][15] The clinical and biochemical features described in the literature are summarized in Table 1. Cultured dermal fibroblasts from patients with this condition have been used to study the underlying molecular defect.…”

“…An explanation confined to the transport or metabolism of glucose may not easily explain the insulin resistance with respect to lipid and lipoprotein metabolism reported in this condition. 12 Kumar et al reported evidence of resistance to the action of insulin in adipose tissue both on intracellular lipolysis, involving hormone-sensitive triglyceride lipase, and on endothelial lipoprotein lipase activity. 12 Severe hypertriglyceridaemia in this case was therefore attributed to both increased production and reduced clearance of triglyceriderich lipoproteins from the circulation.…”

“…12 Kumar et al reported evidence of resistance to the action of insulin in adipose tissue both on intracellular lipolysis, involving hormone-sensitive triglyceride lipase, and on endothelial lipoprotein lipase activity. 12 Severe hypertriglyceridaemia in this case was therefore attributed to both increased production and reduced clearance of triglyceriderich lipoproteins from the circulation. Our patient also had a history of hypertriglyceridaemia and was…”

Pseudoacromegaly—A challenging entity in the endocrine clinic: A systematic review

“…Adult and paediatric endocrinologists may be referred with pseudoacromegaly patients, thus it is important to be aware of this entity and recognize the most common conditions, or at least those that more likely mimicking acromegaly (pachydermoperiostosis and insulin‐mediated pseudoacromegaly). Forty cases (57%) were referred to endocrinologists, predominantly insulin‐mediated pseudoacromegaly cases, which may be explained, at least in part, by the common occurrence of metabolic disorders such as obesity, diabetes or dyslipidemia, while other endocrine‐related issues may also coexist, including amenorrhoea, polycystic ovaries or hirsutism 12,15,20,33–37 . Moreover, the coexistence of tall stature/overgrowth with acromegaloid physical features seem to be more prevalent in insulin‐mediated pseudoacromegaly than in other pseudoacromegaly conditions, which may further explain the increased referrals of such cases to paediatric/adult endocrinologists for the evaluation of excessive growth.…”