PHOENIX – Chronic marijuana use can be a potential cause for hypopituitarism, according to an unpublished case report, which relied on existing data about the effect of cannabis on the hypothalamic-pituitary-gonadal axis.

The case hints at a largely underrepresented problem, researchers said, especially as various states contemplate legalizing marijuana, which is currently the most commonly used illicit drug in the nation, said Dr. Richard Pinsker at the annual meeting of the American Association of Clinical Endocrinologists.

The 37-year-old man arrived at the emergency department of Jamaica (N.Y.) Hospital Medical Center in Queens in late 2012 complaining of shortness of breath, increasing fatigue, and loss of libido. The patient had low blood pressure, and physical examination revealed gynecomastia, bilateral atrophied testis, and bibasilar rales. He disclosed that he had used marijuana daily for 15 years.

After ruling out hemochromatosis, conducting a battery of hormonal tests, and an MRI, Dr. Pinsker and his colleagues diagnosed the patient with hypopituitarism. The culprit? Chronic marijuana use, they concluded after finding no other potential cause.

"I think it’s a thought-provoking study," said Dr. R. Mack Harrell, who will be the president-elect of the AACE this year. "We’ve known for many years, if you use a lot of cannabis, it suppresses the gonadal axis, and it’s been assumed that [cannabis’] only effect was on the gonadal axis. This poster poses the question of whether other pituitary hormones may be affected, and whether every pituitary hormone is at risk, so it’s hypothesis generating."

Dr. Pinsker, who is a practicing endocrinologist and the internal medicine residency program director at Jamaica Hospital Medical Center, said that the finding – and high rate of marijuana use – call for further research on the effect of chronic marijuana use on the endocrine system. He added that that physicians need to do a better job of obtaining a social history from their patients.

Tetrahydrocannabinol, or THC, which is the psychoactive ingredient of marijuana, can alter the hypothalamic-pituitary-gonadal axis either by acting directly on the hypothalamus and altering the gonadotropin-releasing hormone (GnRH) or by altering neural transmitters in the central nervous system, which affect the hypothalamus. The result is lowered luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which lead to reduced testosterone production by Leydig cells of the testis.

Studies have shown cannabis exposure can result in impaired cortisol response to stress. Animal studies have shown that cannabinoids can suppress several hypothalamic-pituitary pathways, including the growth hormone, and the thyroid hormone, reported Dr. Hineshkumar Upadhyay, coauthor of the report.

Meanwhile, THC, which is lipid soluble, can remain stored in the fatty tissue and re-enter the blood stream at very low levels. This pharmacokinetics can cause chronic effect on organ systems even though it is used occasionally, researchers said.

In the case of the 37-year-old patient, researchers first suspected hemochromatosis, which they ruled out by iron studies and echocardiography. Hypopituitarism is rare in young people.

The patient had low levels of LH (0.2 mIU/mL), FSH (1.8 mIU/mL), and testosterone (22 ng/dL). His prolactin levels were high (53 ng/mL), an increase that confirms trouble in the hypothalamic-pituitary axis, said Dr. Pinsker.

Further endocrine chemistry showed that he had adrenocorticotropic hormone (ACTH) of 6 pg/mL and cortisol at 0 mcg/dL. At 60 minutes, following administration of cosyntropin, the levels changed to 6.4 pg/mL and 9.3 mcg/dL, respectively.

Additional tests revealed low levels of total T₃ (30 ng/dL), high T₃ resin reuptake (49%), low total T₄ (3.94 mcg/dL), normal free T₄ (0.97 ng/dL), and low TSH (0.22 mcIU/mL). Growth hormone was within normal limits (5.0 ng/mL), and insulinlike growth factor-1 was low (75 ng/mL; Z-score of –1.3).

MRI showed that the protuberant pituitary gland was slightly larger than the expected size, but there was no identified mass lesion, researchers reported.

Researchers started the patient on replacement hormones – 25 mg cortisone in the morning and 12.5 mg at bedtime, with 25 mcg levothyroxine daily. The patient’s fatigue and edema improved dramatically, they reported. As with other patients who abuse substances, they advised him to stop using marijuana.

Dr. Pinsker, who is also a colonel in the U.S. Army Reserve Medical Corps, said he was planning on collecting more cases before publishing the findings. He added the same mechanism could affect women as well. "We just haven’t looked at it," he said.

"I think it’ll be frightening if the use goes up" as more states make the drug legal "and the awareness does not follow it," he said.

Dr. Pinsker and Dr. Upadhyay had no disclosures.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

Case Report: Chronic marijuana use potential cause for hypopituitarism