Causes of Secondary Hyperhidrosis: Generalized Hyperhidrosis
Generalized hyperhidrosis is usually secondary to an underlying medical condition or can have a physiological basis with heat, humidity, or exercise, leading to excessive sweating out of proportion to thermoregulatory needs. Infections, neoplasia, metabolic and endocrine disorders, high catecholamine states, drug therapy, and neurologic problems can all be associated with systemic hyperhidrosis.[19,119]
Endocrine disorders associated with hyperhidrosis include thyrotoxicosis, hyperpituitarism, diabetes mellitus, pheochromocytoma, hypoglycemia, gout, and menopause. Although heat production increased by the higher metabolic activity of the hyperthyroid state may lead to increased sweating, a significantly increased perspiration rate was not seen in thyrotoxicosis, nor was there an increased sensitivity of eccrine sweat glands to stimuli known to increase secretion. Increased metabolic activity due to hyperpituitarism can lead to increased thermoregulatory sweating. Excessive sweating, tachycardia, and headache in a patient with hyperhidrosis should raise suspicion of pheochromocytoma and prompt measurement of catecholamine levels. The “hot flashes” of menopause can be accompanied by hyperhidrosis due to changing hormone levels.
Acute and chronic infections and neoplasia can lead to fever followed by excessive sweating. Often these conditions are associated with nocturnal diaphoresis, or night sweats. Night sweats can be associated with tuberculosis, endocarditis, other chronic infections, lymphoma, hyperthyroidism, diabetes mellitus, hypoglycemia, systemic vasculitis, pheochromocytoma, carcinoid syndrome, and drug withdrawal. Understanding of the pathogenesis of night sweats associated with many of these illnesses is incomplete, but they may be related to a decrease in hypothalamic temperature setpoint.
Conditions associated with high sympathetic discharge can lead to excessive sweating. These would include respiratory failure, cardiovascular shock and syncope, severe pain, and alcohol or drug withdrawal. Drugs reported to cause hyperhidrosis include propanolol, physostigmine, pilocarpine, tricyclic antidepressants, fluoxetine, venlafaxine, and cyclobenzaprine, but there are more, as well.[19,119] Familial dysautonomia, or Riley-Day syndrome, can lead to generalized hyperhidrosis. A syndrome of episodic hypothermia with hyperhidrosis has been described, due to episodic decreases in the hypothalamic temperature setpoint as part of diencephalic epilepsy. Malformations such as agenesis of the corpus callosum, heterotopia, porencephaly and brainstem nuclei abnormalities, and tumors or surgical manipulation of the hypothalamus have all been implicated in this syndrome. Hyperhidrosis has been seen without hyperthermia in patients with a hypothalamic stroke.
Recognizing that antidepressants can have a side effect of excessive sweating, there has been research in how to mitigate this. For example, a published paper in Current Psychiatry in 2013.1b
Another relevant article was published in 2008 in Drug Safety re. drug-induced hyperhidrosis and hypohidrosis (see ref. 1c).
Useful lists (though not necessarily comprehensive) of drugs/medications and conditions that may cause hyperhidrosis can be found here:
1b. Scarff JR. Options for treating antidepressant-induced sweating. Current Psychiatry 12:1 (2013): 51.
1c. Cheshire WP, Fealey RD. Drug-induced hyperhidrosis and hypohidrosis. Drug Safety 31:2 (2008): 109-126.