Clinical Overview > Condition/ Syndrome
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Summary
A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose–fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail.
Learning points
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There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians.
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GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient.
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The Randle cycle, or glucose–fatty acid cycle, outlines the mechanism for this acute relationship.
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Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.
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Summary
A 46-year-old woman presented multiple times in a 4-month period with hypotension, sepsis, hypoglycaemia and psychosis. A low random cortisol in combination with her presenting complaint made adrenal insufficiency the likely diagnosis. Fluid resuscitation and i.v. steroid therapy led to clinical improvement; however, a short synacthen test (SST) demonstrated an apparently satisfactory cortisol response. The test was repeated on a later admission and revealed a peak cortisol level of 25 nmol/l (>550 nmol/l). Concurrent treatment with i.v. hydrocortisone had led to a false-negative SST. ACTH was <5 ng/l (>10 ng/l), indicating secondary adrenal failure. We discuss the challenges surrounding the diagnosis of adrenal insufficiency and hypopituitarism, the rare complication of psychosis and a presumptive diagnosis of autoimmune lymphocytic hypophysitis (ALH).
Learning points
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Adrenocortical insufficiency must be considered in the shocked, hypovolaemic and hypoglycaemic patient with electrolyte imbalance. Rapid treatment with fluid resuscitation and i.v. corticosteroids is vital.
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Polymorphic presentations to multiple specialities are common. Generalised myalgia, abdominal pain and delirium are well recognised, psychosis is rare.
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A random cortisol can be taken with baseline bloods. Once the patient is stable, meticulous dynamic testing must follow to confirm the clinical diagnosis.
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The chronic disease progression of ALH is hypothesised to be expansion then atrophy of the pituitary gland resulting in empty sella turcica and hypopituitarism.
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If hypopituitarism is suspected, an ACTH deficiency should be treated prior to commencing thyroxine (T4) therapy as unopposed T4 may worsen features of cortisol deficiency.
