mitotane and Adrenal Gland Hypofunction studies

Mitotane: A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression.

Research Excerpts

Excerpt	Relevance	Reference
"Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities."	5.46	Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma-A New Look at an Old Drug. ( Chou, J; Gerst, S; Gopalan, A; Hrabovsky, A; Kampel, L; Katz, S; Kelly, C; Lung, B; Raj, N; Reidy-Lagunes, DL; Saltz, LB; Untch, BR, 2017)
"ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management."	2.44	Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. ( Bertagna, X; Bertherat, J; Biller, BM; Boscaro, M; Buchfelder, M; Colao, A; Grossman, AB; Hermus, AR; Hofland, LJ; Klibanski, A; Lacroix, A; Lindsay, JR; Melmed, S; Newell-Price, J; Nieman, LK; Petersenn, S; Sonino, N; Stalla, GK; Stewart, PM; Swearingen, B; Vance, ML; Wass, JA, 2008)
"Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities."	1.46	Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma-A New Look at an Old Drug. ( Chou, J; Gerst, S; Gopalan, A; Hrabovsky, A; Kampel, L; Katz, S; Kelly, C; Lung, B; Raj, N; Reidy-Lagunes, DL; Saltz, LB; Untch, BR, 2017)
"UA induced remission of hypercortisolism in all patients, with sustained significant clinical improvement."	1.42	Unilateral Adrenalectomy as a First-Line Treatment of Cushing's Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia. ( Benoit, M; Caron, P; Chabre, O; Chaffanjon, P; Debillon, E; Lambert, B; Massoutier, M; Salenave, S; Tabarin, A; Velayoudom-Cephise, FL; Wagner, T; Young, J, 2015)
"Both patients developed hypoadrenalism while on o,p'-DDD and apparently adequate dexamethasone replacement therapy."	1.27	The effect of o,p'-DDD on adrenal steroid replacement therapy requirements. ( Hales, IB; Henniker, AJ; Ho, K; Luttrell, BM; Robinson, BG; Smee, IR; Stiel, JN, 1987)

Research

Studies (11)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Number of Participants That Experience Changes in Clinical Signs of Hypercortisolemia

Timeframe	Studies, this research(%)	All Research%
pre-1990	4 (36.36)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (18.18)	29.6817
2010's	4 (36.36)	24.3611
2020's	1 (9.09)	2.80

Authors	Studies
Muratori, L	1
Pia, A	1
Reimondo, G	1
Pisano, C	1
La Salvia, A	1
Puglisi, S	1
Scagliotti, GV	1
Sperone, P	1
Reidy-Lagunes, DL	1
Lung, B	1
Untch, BR	1
Raj, N	1
Hrabovsky, A	1
Kelly, C	1
Gerst, S	1
Katz, S	1
Kampel, L	1
Chou, J	1
Gopalan, A	1
Saltz, LB	1
Debillon, E	1
Velayoudom-Cephise, FL	1
Salenave, S	1
Caron, P	1
Chaffanjon, P	1
Wagner, T	1
Massoutier, M	1
Lambert, B	1
Benoit, M	1
Young, J	1
Tabarin, A	1
Chabre, O	1
Weigel, M	1
Hahner, S	1
Sherlock, M	1
Agha, A	1
Behan, LA	1
Stewart, PM	2
Arlt, W	1
Beier, D	1
Frey, K	1
Zopf, K	1
Quinkler, M	1
De Francia, S	1
Ardito, A	1
Daffara, F	1
Zaggia, B	1
Germano, A	1
Berruti, A	1
Di Carlo, F	1
BLEDSOE, T	1
ISLAND, DP	1
NEY, RL	1
LIDDLE, GW	1
Biller, BM	1
Grossman, AB	1
Melmed, S	1
Bertagna, X	1
Bertherat, J	1
Buchfelder, M	1
Colao, A	1
Hermus, AR	1
Hofland, LJ	1
Klibanski, A	1
Lacroix, A	1
Lindsay, JR	1
Newell-Price, J	1
Nieman, LK	1
Petersenn, S	1
Sonino, N	1
Stalla, GK	1
Swearingen, B	1
Vance, ML	1
Wass, JA	1
Boscaro, M	1
Opitz, M	1
Lettow, E	1
Loppnow, H	1
Grevel, V	1
Pardo, C	1
Boix, E	1
López, A	1
Picó, A	1
Besser, GM	1
Jeffcoate, WJ	1
Robinson, BG	1
Hales, IB	1
Henniker, AJ	1
Ho, K	1
Luttrell, BM	1
Smee, IR	1
Stiel, JN	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Metabolic, Pressor and Neuropsychological Effects of Metyrapone Treatment in Patients With Hypercortisolism[NCT05255900]		20 participants (Anticipated)	Observational	2022-04-28	Recruiting
Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine[NCT02160730]	Phase 2	4 participants (Actual)	Interventional	2014-05-31	Terminated (stopped due to NIH grant ended.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The number of participants that achieved a urinary free cortisol level above the upper limit of the normal range but reduced by ≥50% from baseline at week 4. (NCT02160730)
Timeframe: Baseline, Week 4

Number of Participants That Have a Visible Change in Tumor Size

Intervention	Participants (Count of Participants)
R-roscovitine	2

A visible change in tumor size as determined by the investigator after reviewing MRI reports between baseline and 4 weeks of treatment. (NCT02160730)
Timeframe: Baseline, 4 weeks

Number of Participants With a Normalized 24 Hour Urinary Free Cortisol After 4 Weeks

Intervention	Participants (Count of Participants)
R-roscovitine	0

"To evaluate the efficacy of R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks on normalizing 24 hour urinary free cortisol (24 h UFC) levels in CD patients. Normalizing is defined as having urine free cortisol levels within the normal range for that lab value." (NCT02160730)
Timeframe: Baseline, 4 weeks

Number of Participants With Adverse Events

Intervention	Participants (Count of Participants)
R-roscovitine	0

The number of participants that experience an adverse event between baseline and study end likely related to study drug as a measure of safety and tolerability. (NCT02160730)
Timeframe: Baseline, 4 weeks

Change in Clinical Symptoms

Intervention	Participants (Count of Participants)
R-roscovitine	2

Change in typical Cushing's syndrome clinical signs and symptoms defined by mean weight at baseline and 4 weeks. (NCT02160730)
Timeframe: Baseline, 4 weeks

Change in Diastolic Blood Pressure

Intervention	lbs (Mean)
	Baseline	4 Weeks
R-roscovitine	217	217.4

Mean diastolic blood pressure between baseline and 4 weeks. (NCT02160730)
Timeframe: Baseline, 4 weeks

Change in Mean HbA1c Levels Between Baseline and 4 Weeks

Intervention	mmHg (Mean)
	Baseline	4 Weeks
R-roscovitine	76.5	71

HbA1c levels are measured at baseline and at study end, these are averaged across all subjects. (NCT02160730)
Timeframe: Baseline, 4 Weeks

Change in Systolic Blood Pressure

Intervention	Percentage (Mean)
	Baseline	Study End-4 weeks
R-roscovitine	6.9	7

Mean change in systolic blood pressure between baseline and 4 weeks. (NCT02160730)
Timeframe: Baseline, 4 weeks

Changes in Serum Cortisol Between Baseline and 4 Weeks

Intervention	mmHg (Mean)
	Baseline	4 weeks
R-roscovitine	150.3	128.3

Mean serum cortisol values at baseline and 4 weeks (NCT02160730)
Timeframe: Baseline, 4 weeks

Fasting Glucose at Baseline and 4 Weeks

Intervention	mg/dL (Mean)
	Baseline	4 Weeks
R-roscovitine	25.6	27.1

Mean change between baseline and week 4 of fasting blood glucose levels. (NCT02160730)
Timeframe: Baseline, 4 Weeks

Plasma ACTH at Baseline and 4 Weeks

Intervention	g/dL (Mean)
	Baseline	4 weeks
R-roscovitine	121.4	104.3

Mean change in Plasma ACTH between baseline and 4 weeks. (NCT02160730)
Timeframe: Baseline, 4 weeks

Article	Year
Mitotane treatment for adrenocortical carcinoma: an overview. Minerva endocrinologica, 2012, Volume: 37, Issue:1 Topics: Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenalectomy; Antineoplastic Agents, Hormonal; Ant	2012
Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. The Journal of clinical endocrinology and metabolism, 2008, Volume: 93, Issue:7 Topics: ACTH Syndrome, Ectopic; Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone; Cushing S	2008

Article	Year
Prolonged Adrenal Insufficiency After the Discontinuation of Mitotane Therapy. Endocrine, metabolic & immune disorders drug targets, 2020, Volume: 20, Issue:3 Topics: Adrenal Insufficiency; Adult; Antineoplastic Agents, Hormonal; Humans; Male; Mitotane; Withholding T	2020
Complete Responses to Mitotane in Metastatic Adrenocortical Carcinoma-A New Look at an Old Drug. The oncologist, 2017, Volume: 22, Issue:9 Topics: Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenocortical Carcinoma; Adult; Aged; Aged, 80 and	2017
Unilateral Adrenalectomy as a First-Line Treatment of Cushing's Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia. The Journal of clinical endocrinology and metabolism, 2015, Volume: 100, Issue:12 Topics: Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adrenalectomy; Adrenocorticotropic Hormone;	2015
Immediate versus modified release hydrocortisone in mitotane-treated patients with adrenocortical cancer. Clinical endocrinology, 2017, Volume: 86, Issue:4 Topics: Adrenal Cortex Neoplasms; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Aged; Case-Cont	2017
AN EFFECT OF O,P'-DDD ON THE EXTRA-ADRENAL METABOLISM OF CORTISOL IN MAN. The Journal of clinical endocrinology and metabolism, 1964, Volume: 24 Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Addison Disease; Adrenal Insufficiency; Adrenalectomy; A	1964
[Experiences with Lysodren treatment of Cushing's syndrome in dogs]. Tierarztliche Praxis, 1983, Volume: 11, Issue:4 Topics: Adrenal Insufficiency; Animals; Central Nervous System Diseases; Cushing Syndrome; Dog Diseases; Dog	1983
[Adrenal crisis due to mitotane therapy]. Medicina clinica, 2002, Mar-02, Volume: 118, Issue:7 Topics: Adrenal Insufficiency; Adult; Antineoplastic Agents, Phytogenic; Female; Humans; Mitotane	2002
Endocrine and metabolic diseases. Adrenal diseases. British medical journal, 1976, Feb-21, Volume: 1, Issue:6007 Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenal Gland Neoplasms; Adrenal Insuffici	1976
The effect of o,p'-DDD on adrenal steroid replacement therapy requirements. Clinical endocrinology, 1987, Volume: 27, Issue:4 Topics: Adrenal Gland Neoplasms; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Dexamethasone; F	1987

mitotane and Adrenal Gland Hypofunction