A tale of two sisters - delayed diagnosis of genetic hyperinsulinaemic hypoglycaemia.

Summary: Congenital hyperinsulinism is the leading cause of persistent hypoglycaemia in infants and children; however, it is uncommon to be diagnosed in adulthood. We describe the cases of two sisters who presented with hyperinsulinaemic hypoglycaemia aged 47 and 57 years old, who were subsequently diagnosed with compound heterozygous likely pathogenic variants in the ABCC8 gene, a known cause of monogenic congenital hyperinsulinism. We discuss the typical presenting features, investigation findings, and treatment strategies for patients with this condition. Learning Points: Congenital hyperinsulinism is a rare cause of hyperinsulinaemic hypoglycaemia diagnosed in adulthood. Clinical presentation is similar to an insulinoma, and imaging modalities may assist in differentiation. There are minimal medical therapies currently available for patients non-responsive to diazoxide (such as those with ABCC8 and KCNJ11 variants). Continuous glucose monitoring can be helpful in giving patients autonomy in managing their disease, as well as relieving anxiety and fear associated with hypoglycaemia.

Postmenopausal hormone therapy: from monkey glands to transdermal patches.

The climacteric is not a condition of the modern age, although with increased life expectancy over the centuries, more women will experience this physiological transition. As women are living longer there is a greater expectation that good health will be maintained through to the late decade. Thus the potential long-term adverse health consequences of using hormonal therapies (HTs) to alleviate menopausal symptoms are of considerable concern for women and medical practitioners. This concern is often the basis for a decision whether or not to use HT. We have reviewed the history of knowledge of the menopause and the development of HT for the treatment of climacteric complaints. We have also summarised the current evidence for specific benefits and risks of HT. Data indicate that postmenopausal HT is appropriate for the management of vasomotor symptoms, but that HT should not be prescribed for the prevention of cardiovascular disease or dementia. HT does prevent bone loss and osteoporotic fracture; however, use for this purpose remains controversial. The risk of breast cancer with HT varies according to the preparation used, such that oestrogen without concurrent progestin appears to convey little, or possibly even no significant breast cancer risk. There is insufficient information regarding the long-term use of non-oral HT, low-dose HT or novel compounds such as tibolone or the selective oestrogen receptor modulators with respect to breast cancer and cardiovascular risk for specific recommendations to be made.

Androgen insufficiency in women: diagnostic and therapeutic implications.

The proposed key symptoms of the female androgen insufficiency syndrome (FAIS) include reduced libido, diminished well being and lowered mood. The diagnosis of FAIS is made on the basis of these symptoms in the setting of a low serum free testosterone level. However, there is currently no readily available inexpensive assay which reliably measures free testosterone levels in the female range. The diagnosis of FAIS is further complicated by the lack of data demonstrating a minimum serum free testosterone level which, if below this, correlates with the symptoms of FAIS. Despite the complexities involved with defining FAIS, the symptoms have been reported to respond well to testosterone replacement. There is a need for formulations of testosterone therapy specifically designed for use in women, along with clear guidelines regarding optimal therapeutic doses and long-term safety data.

Postmenopausal hormone therapy: the pros and cons.

The use of postmenopausal hormone therapy (HT) has recently generated much debate following the results of various large randomised controlled trials. This has challenged physicians to reassess the use of HT in each individual woman within the realm of her symptomatology and risk profile for long-term illnesses. There are several areas of definite benefit or risk and many areas of uncertainty. The results of recent randomised controlled trials pertain to the specific HT regimens used and the characteristics of the study groups, such that the conclusions cannot be extrapolated to the use of HT in general.