I read a ton of scientific literature for my job, and usually its some really great research. Sometimes, however, I get gems like this:

Lancet. 2009 Apr 11;373(9671):1310. doi: 10.1016/S0140-6736(09)60508-0.

Where are my testes?

Kumar S, Kanthan A, Abraham RD.
Department of Cardiology, Division of Medicine, Westmead Hospital, Sydney, New South Wales, Australia.

In October, 2007, a 42-year-old man presented to us with pleuritic chest pain similar to his previous presentations of recurrent pulmonary emboli (PE). He was poorly compliant to warfarin prescribed for a diagnosis of heterozygous factor V Leiden deficiency 3 years previously. The most recent PE (July, 2006) was from self-cessation of warfarin a year ago for a period of 4 months. On examination he had bilateral painful gynaecomastia. On detailed questioning, he reported reduced libido and relationship problems which had evolved over the past year. Over the same period he also noted a continuous dull testicular ache, with gradual reduction in the size of his testes to the point that he could no longer feel them, painful gynaecomastia, erectile dysfunction, and reduced facial and body hair growth. He was an ex-military serviceman and had previously been well-built, but had noticed a gradual reduction in muscle bulk over a year. This constellation of symptoms had caused him much distress. There was no history of trauma. He was a non-smoker and did not drink alcohol. There was a history of clotting disorders in the family but he was unaware of the specific diagnoses. As a computing graduate, he was currently running a business from home. His general practitioner had prescribed a testosterone patch, which had helped, but he did not attend follow-up regularly. He had no features suggestive of an endocrinopathy, pituitary enlargement, or Klinefelter syndrome. Examination showed scarcity of facial, chest, and pubic hair, reduced muscle bulk, bilateral gynaecomastia, small—almost impalpable—testes and no abdominal organomegaly. Primary hypogonadism was confirmed with high luteinising hormone (25·1 IU/L) and follicular stimulating hormone (43 IU/L), and low serum testosterone at 7·9 nmol/L (normal range 8–26). Heterozygous factor V Leiden mutation was re-confirmed on testing with absence of other concurrent thrombophilias.

His international normalised ratio (INR) on presentation was 1·8—clearly subtherapeutic for someone with a thrombophilia. Investigations for chest pain were normal. Testicular ultrasonography showed small (1·5 cm) and heterogeneous echo-texture of both testes. There was absent flow in the testicular veins with central echoes and prominent vessel dilatation consistent with bilateral venous thromboses (figure). His primary hypogonadism was most likely related to bilateral venous infarction from subtherapeutic anticoagulation for thrombophilia, although an additional underlying predisposition could not be excluded. Depot testosterone was started with reported improvement in libido shortly thereafter, and we urged strict adherence to anticoagulation therapy. Regular counselling and karyotyping for Klinefelter syndrome was planned; however, the patient did not present for regular follow-up. When we last saw the patient in July, 2008, he had noted substantial improvement in potency and libido with depot testosterone.

Primary hypogonadism is rarely caused by testicular infarction as a result of torsion, blunt trauma, epididymoorchitis, sickle cell disease, Wegener's granulomatosis,1 or inherited thrombophilias.2, 3 and 4 Factor V Leiden has a prevalence of up to 5% and confers a four- to eight-times increase in the risk of deep venous thromboses; by itself the condition is only a mildly hypercoagulable state. The presence of concurrent thrombophilias or environmental factors, such as surgery or immobility, may increase the risk. Klinefelter syndrome, or its mosaicism, occurs in one in 500 men and is a common cause of primary hypogonadism. Its clinical features can be subtle, can present across a broad spectrum of phenotypes,5 and can be associated with clotting tendencies because of hypofibrinolysis from androgen deficiency.4 Our case highlights the value of listening to and observing patients carefully. The importance of strict anticoagulation to prevent major organ infarction in patients with high-risk thrombophilic disorders could not be more painfully emphasised.