Too hot to handle

I am currently caring for two patients, a man and a woman in their 60s (not related to each other and to my knowledge unaware of each other), who complain of intolerable episodes of disabling hot spells. I — and several colleagues from a wide array of specialties — am having trouble coming up with either a diagnosis or an effective treatment plan.

The man felt nonspecifically unwell and his primary care physician, finding no specific diagnosis, ordered a stress test which the patient passed. Two days later he presented to the ER with vague symptoms again, but this time he underwent an urgent coronary artery bypass grafting because of the findings in the ER. Not his lucky month because two days after his discharge one of the grafted vessels closed and stents were placed. It was about a week later when he began to complain of episodes of feeling extremely hot without any particular pattern. He did become flushed, but there was no perspiration and he did not feel warm to the touch. His wife of 50 years had experienced and not forgotten her own menopausal symptoms and felt that his complaints did not resemble what she recalled. Over the next several months he has undergone extensive evaluation by a number of specialists to systematically rule out allergy to stents, pheochromocytoma, carcinoid, mastocytosis, hyperthyroidism, hypogonadism — and I am sure I have left off other unusual conditions that were considered. He does not have diabetes and does not have gustatory sweating (feelings of intense heat associated with eating).

He has mild Parkinson’s disease, but I could not find any literature support for a link between that disease and hot flashes/flushes. He was clinically euthyroid by history and examination, confirmed by lab studies. He was clinically eugonadal again by history and examination, but his total serum testosterone was at the low end of normal at 300 ng/mL (reference interval 270-850 ng/mL). Since he was in such distress and had not found any medication to provide relief, I decided to try transdermal testosterone in a low dose but to no avail. While on this therapy, I suggested he try an over-the-counter soy product, but this too was not successful.

What are we all missing? What next to study? What is the next possible therapy?

The woman of this series is equally puzzling. She remembers, and none too fondly, her menopause transition, but that quickly resolved with estrogen replacement and she discontinued this about 10 years ago. The current symptoms are quite different in her estimation in that they are not associated with any external signs, do not occur at night and are not associated with either sweating or flushing. In fact they are not even hot flashes. At various times of the day, unrelated to activity or meals, she has an overpowering sensation of heat throughout her trunk and arms, occasionally affecting her legs. No physician who has examined her has documented any objective evidence of disease, and her extensive laboratory work-up has been negative. She has been prescribed a variety of psychotropic drugs without benefit, but at times she feels so overwhelmed by her symptoms that she gets relief from lorazepam although this does not relieve the symptoms of feeling hot.

She has no personal or family history of breast cancer, cardiovascular or thromboembolic disease, and I will have her try a course of estrogen therapy again. But not until I see the results of a mammogram since she is so many years post-menopause. All annual mammograms until now have been normal, but if the WHI study taught us anything, it is that estrogen therapy is safest when begun as early as possible in menopause. Menopausal symptoms are extremely variable with respect to duration and severity, but I have not previously seen a recurrence of such symptoms after such a long estrogen-free period. Besides, she is convinced that these symptoms are quite different to those she experienced before.

It is not uncommon to encounter patients with disabling symptoms without objective evidence of disease. It is too easy (and regrettably too common) to dismiss them as psychosomatic illnesses, but my gut tells me that these two patients have something wrong that we are all missing.