Q:   When a patient who has not had cortisol testing yet but describes the way they feel as “adrenaline surges” or “raging cortisol”, is there anything else that could be causing a symptom like this?

A:   There are many conditions that can give “up and downs”, “spells”, flushes, anxiety and a thorough history should be taken before going on the path of evaluation for elevated cortisol or something else.

Fluctuations in the blood sugars, change in sleep, “adrenergic spells” either in the setting of dysautonomia or pheochromocytoma, carcinoid, medullary thyroid cancer, mastocytosis can give surges but most of the times it is not something as serious.  (Dr. Georgiana Dobri, Cornell)

A:   In general, cortisol levels are consistently increased in patients with clear-cut Cushing’s syndrome.  In that situation, the differences in minute to minute cortisol levels (relative to the average value) is small and we would not expect the patient to experience any symptoms as a consequence of that specific increase.  Some patients experience headache when their blood pressure is very high and may characterize this as a surge. Other patients become irritable and fly off the handle when they have Cushing’s syndrome, and this might be interpreted as a “rage” due to cortisol.  Also, some patients with cyclic Cushing’s syndrome have increased symptoms when their cortisol levels are high, compared to how they feel when the values are normal or low. Patients who experience symptoms of a “surge”, “rush”, or “rage” should bring this up to an experienced endocrinologist, who will consider these along with other symptoms, when evaluating whether Cushing’s syndrome or some other disorder is present.  (Dr. Lynnette Nieman, NIH)

A:   We usually define cortisol or adrenaline abnormalities by hormone measurements outside normative ranges. The episodic symptoms described as “surges” or “raging hormones” can be caused by multiple conditions, both endocrine and non-endocrine. I would start is with an evaluation by an internist and/or a general endocrinologist.  (Dr. Adriana Ioachimescu, Emory University Hospital)

Q:   Can you have polycystic ovarian syndrome (PCOS) and Cushing’s at the same time?  Can you resolve one by treating the other?

A:   Yes – PCOS is significantly influenced by the genetic makeup of the patient. The weight gain which generally occurs in patients with Cushing’s will often aggravate the symptoms that women with PCOS frequently have (irregular periods, facial hair growth, acne, scalp hair loss). Conversely, weight loss, which may occur after successful treatment of Cushing’s, will often help improve symptoms associated with PCOS. (Dr. Nicholas Tritos, Massachusetts General Hospital)

A:   Yes, PCOS and Cushing’s frequently coexist in women. Unfortunately, many patients with Cushing’s are told initially that they have PCOS and thus diagnosis of Cushing’s could be delayed. The opposite could be also true, PCOS can falsely induce elevation in cortisol measurements and misdiagnose a patient as having Cushing’s.

Due to overlapping signs and symptoms, patients need to have a proper differential diagnosis, and if they have both diseases, treat both accordingly. In a woman with Cushing’s, treatment of Cushing’s might resolve symptoms and improve the features of PCOS.  (Dr. Maria Fleseriu, Oregon Health and Science University)

A:   The important issue here is a correct diagnosis, which would allow the physician to discern one diagnosis from the other and recommend appropriate treatment. Both conditions affect predominantly premenopausal women and can cause problems with ovulation and menstrual periods, excess face hair and acne, weight gain, high glucose, and high blood pressure. PCOS is much more prevalent and lacks some of the signature manifestations of Cushing’s syndrome, such as purple stretch marks, easy bruising, muscle weakness and osteoporosis. However, the presentation varies from one case to another and sometimes the characteristic features of high cortisol are subtle. The good news here is that endocrinologists can do the tests and differentiate between the two conditions.  (Dr. Adriana Ioachimescu, Emory University Hospital)

Q:   I’ve been treating a prolactinoma for many years with cabergoline, with acceptable but not great results.  I’ve even gone off the medication several times when it didn’t even seem to be stopping the galactorrhea I’ve had since diagnosed.  Recently I’ve noticed that I’m experiencing many symptoms that look like Cushing’s.  Can a prolactinoma grow or cause problems or even Cushing’s?

A:   Although uncommon, it is occasionally possible for some pituitary adenomas to produce both prolactin and ACTH. The endocrinologist can test for the presence of Cushing’s in your case. If the tumor is producing both ACTH and prolactin, then pituitary surgery should be discussed with an experienced pituitary neurosurgeon. Some patients whose tumors produce only prolactin may also benefit from pituitary surgery, if they cannot tolerate cabergoline or bromocriptine or if the medications are not effective (for example, if the tumor grows despite adequate treatment with medication). A discussion with an experienced endocrinologist would be advised in order to discuss these options in depth.  (Dr. Nicholas Tritos, Massachusetts General Hospital)

A:   Prolactin elevation and galactorrhea could be multifactorial. In large tumors, prolactin elevation can be due to stalk effect and Cabergoline is not efficient in making the tumor smaller, though is resolving galactorrhea in most cases. It is important to also look at concomitant medications that can raise prolactin. Sometimes, though rarely, even a prolactinoma will not respond at all to cabergoline and patients will need surgery in these cases to resolve the hyperprolactinemia and tumor effects.

Patients with pituitary tumors who have signs and symptoms of Cushing’s need formal assessment to rule out Cushing’s.  (Dr. Maria Fleseriu, Oregon Health and Science University)

A:   An evaluation by a pituitary endocrinologist is necessary in cases of suboptimal response to dopamine agonists of tumors thought to secrete prolactin. There are several circumstances when surgery is considered, such as when there is resistance to medical treatment with dopamine agonists. The tumor appearance on the MRI and prolactin levels should be considered along with the clinical context. Other medications can interfere with the effect of dopamine agonists and should be carefully evaluated. 

Patients with hyperprolactinemia can experience weight gain, increased face and body hair, mood changes and abnormal bone mineral density, which are also manifestations of high cortisol. However, patients with prolactinomas do not usually have purple stretch marks, easy bruising, muscle weakness or significant changes in appearance. There are rare situations when a pituitary adenoma can secrete both prolactin and ACTH, or when two different pituitary adenomas are present in the same patient. Our group published an “intriguing case of a double pituitary adenoma” in the journal World Neurosurgery in 2019 (Gonzalez A et al) which gave us the opportunity to review the literature published on this topic.  (Dr. Adriana Ioachimescu, Emory University Hospital)

If you would like to read about this case of a patient who was first treated for possible lupus but was ultimately found to have both a prolactinoma and an ACTH-producing adenoma, visit this url or scan the QR code: https://csrf.net/wp-content/uploads/2021/08/double-adenoma-case-World-Neurosurgery-2019.pdf