My 26 year old daughter was diagnosed with Grave’s disease [a autoimmune thyroid condition], insulin resistance and 3 beta HSD non-classic adrenal hyperplasia (CAH). She has had Acanthosis Nigricans for at least 10 years. Six months before the diagnoses of Graves’ disease, her TSH was normal. The Grave’s disease appeared after a bout with pneumonia. How severely does Grave’s aggravate insulin resistance? Can insulin resistance aggravate Grave’s? Does CAH have an effect on insulin resistance and/or Grave’s?

It sounds like your daughter’s case is somewhat complicated. She has been diagnosed with three separate, problems, which although certainly could happen, makes you wonder if you can’t somehow relate at least two of them.

I assume that your daughter is overweight and/or has some features of excess androgens (hormones that cause acne, pubic hair, hair under the chin, on the abdomen and chest and can also cause irregular periods). I don’t know if your daughter’s blood sugars were abnormal before the diagnosis of Grave’s disease (overactive thyroid) or now that her thyroid is overactive.

Let me try to relate at least two of these diagnosis. It is possible that your daughter does not have 3 Beta Hydroxysteroid deficiency. This is caused by a mild deficiency of one of the chemicals (enzymes) that helps control the synthesis of cortisol in the adrenal gland. If someone has a mild deficiency of this enzyme, they can make enough cortisol to be healthy, but may make too much DHEA, an androgen made by the adrenal gland. This is because the healthy pituitary in the brain has to make extra ACTH to push the adrenal gland to make enough cortisol. When this happens, the adrenal gland winds up making too much DHEA. There are specialized tests to diagnose this specific hormonal problem, such as giving the person a shot of synthetic ACTH and measuring the rise of many hormones made by the adrenal gland. DHEA and another hormone 17OH pregnenolone go up “too high” compared to other hormones.

This is a fairly rare disorder, not directly related to either insulin resistance or Grave’s disease. There is also a wide range of normal 17OH pregnenolone and DHEA responses, and for years endocrinologists have argued what are the upper limits of normal. This is important, because treating with a small dose of cortisol can easily control the abnormal androgens and side effects.

Sometimes it is difficult to tell the difference between a mild adrenal enzyme deficiency and “polycystic ovary syndrome” (PCO or PCOS). The latter condition is a poorly understood metabolic imbalance associated with a variety of abnormalities including excess androgens, benign cysts in the ovaries, obesity, irregular periods, hypertension, and insulin resistance/type 2 diabetes. You don’t have to have all the above to have the syndrome and endocrinologists are still arguing what are the minimum criteria. You don’t even have to have cysts on the ovaries to have polycystic ovary syndrome. This syndrome is not associated with Grave’s disease, but can be caused by untreated underactive thyroid (and respond to treatment with thyroid hormone) or can be caused by an untreated adrenal enzyme deficiency such as 3 Beta Hydroxysteroid deficiency. In the past, “non specific” treatment of PCO has included treatment with oral contraceptives, small doses of cortisol (even if the person does not have a specific adrenal enzyme deficiency), or the weak blood pressure medication spironolactone which counteracts the affect of the excess androgens. Recently, treatment with the newer oral anti-diabetic agents such as metformin and troglitazone which increase insulin sensitivity (decrease insulin resistance) have also found to be helpful, even if the person does not have high blood sugars. Most of these people have high insulin levels even if their blood sugar is normal (insulin resistance) as seen in most overweight individuals.

The thickening and darkening of the skin (acanthosis nigricans) is usually seen in overweight individuals with severe insulin resistance with or without high blood sugars.

Autoimmune thyroid problems (overactive or underactive thyroid) are more common in individuals with type 1 diabetes (insulin deficiency), not more common in type 2 diabetes. However, since autoimmune thyroid problems and type 2 diabetes/obesity/insulin resistance are very common in the general population, there are bound to be people with both conditions even though they aren’t directly related. Excess thyroid hormone levels also interfere with insulin action (cause insulin resistance), and can raise the blood sugars further is someone with type 2 diabetes or cause high blood sugars in someone with insulin resistance whose blood sugars were normal previously if they can’t make enough insulin to overcome the added insulin resistance.

Adrenal enzyme deficiencies are autosomal recessive disorders unrelated to either autoimmune thyroid disease or insulin resistance/ type 2 diabetes/ polycystic ovary syndrome. It is possible to have all three. The only reason to differentiate between an enzyme deficiency and polycystic ovary syndrome is because the genetics and treatment options might be slightly different (though both low dose steroids and spironolactone are used to treat both conditions).

I hope this wasn’t too complicated and helps you understand the complexity of your daughter’s situation.

TGL